GX P Q UA L I T Y M A N UA L D R A F T D O C U M E N T F O R C O M M E N T V E R S I O N 1.

GXP Quality Manual

Draft Document for Comment
Version 1.0

Presented for comment March 2009

COPYRIGHT 2009 ENKAP

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We Welcome Your Comments!

Invitation to Contribute Your Expertise

GXP Quality Manual
Draft Document for Comment
Version 1.0
enKap is pleased to offer you the opportunity to contribute your expertise by considering
your comments related to the following areas of this draft document:
Accuracy
Clarity
Organization
Adequacy of detail
Additional subject areas
Usability
Industry References - Regulations, Guidelines, Standards, etc
Incorporating comments into Version 2.0 of this document is our main objective. Our
faculty of Subject Matter Experts (SMEs) will review all comments and suggestions for
consideration in Version 2.0.
We look forward to your response.
Thank you for your consideration.
Glenn Melvin
President
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Draft Document For Comment

GXP Quality Manual

Table of Contents
1. EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2. DEFINITIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
3. MANAGEMENT RESPONSIBILITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
4. QUALITY COUNCIL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
5. QUALITY SYSTEM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
6. CONTRACT REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
7. DESIGN CONTROL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
8. DOCUMENT CONTROL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
9. PURCHASING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
10. PRODUCT IDENTIFICATION AND TRACEABILITY. . . . . . . . . . . . . . . . . . . . . . . . . . . 10
11. PROCESS CONTROL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
12. INSPECTION AND TESTING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
13. CONTROL OF INSPECTION, MEASURING AND TEST EQUIPMENT . . . . . . . . . . . . 11
14. INSPECTION AND TEST STATUS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
15. CONTROL OF NON-CONFORMING PRODUCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
16. CORRECTIVE AND PREVENTATIVE ACTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
17. CONTROL OF QUALITY RECORDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
18. INTERNAL QUALITY AUDITING. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
19. TRAINING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
20. RISK ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
21. STATISTICAL TECHNIQUES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

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1. EXECUTIVE SUMMARY
Purpose
The world pharmaceutical market is increasingly competitive as more new products are launched and
governments continue to exert downwards pressure on healthcare costs. The ability to succeed in this
business environment depends, in part, on a companys ability to supply products that consistently
satisfy customer expectations with respect to efficacy, safety, and quality, and to deliver them on time.
Achievement of this goal requires adherence to the highest standards of quality in all the activities
necessary to discover, develop, manufacture and supply products.
Principles of quality management have been adopted that ensure that employees and third-party
contractors routinely comply with the requirements of regulatory authorities, satisfy customer
expectations and minimize costs. These principles of quality management are based on the philosophy of
correct the first time.
This Quality Manual is intended as supplementary to other quality-based operating principles, and
provides an overview of the state of affairs, from a quality assurance department standpoint. The
established quality system and approach to quality serves as the cornerstone of current and future
success of the company. The company will be a cost effective and consistent supplier of pharmaceutical
products only when integrated quality principles and standards have been integrated in as part of daily
business activities.
This Quality Manual is a documented overview of the efficacy of the established quality system, and
serves as a conduit for the identification and ultimate implementation of continuous improvement
initiatives.
A Corporate Quality Policy has also been established, which is intended to serve as the framework for
continuous improvement within the organization, and to manage quality objectives with third-party GXP
subcontractors, as well as meet expectations for quality. The Quality Manual authorizes and governs the
creation of subsidiary quality-related documentation, as promulgated by Standard Operating Procedures
(SOPs), guidelines and policies as they relate to GXP operational areas throughout the organization. This
Quality Manual is based on general principles of ISO 9000 and 21 CFR 820, but also include exceptions
and additions where deemed appropriate, based on the requirements of quality for a GXP operating
environment. The requirements and quality standards addressed in this quality manual are intended to
meet the requirements of the regulations which govern good practice in the conduct of clinical studies,
non-clinical studies, and clinical and commercial manufacturing operations.
Scope
The Quality Manual applies to all company functions, duties, activities, and responsibilities, including the
use of third-party operations which perform GXP operational tasks that affect the quality of manufactured
pharmaceutical products, nonclinical studies and clinical studies sponsored by the company
Review and Control
The Quality Manual will be reviewed and re-issued annually to ensure that current operational qualitybased practices and processes remain aligned with set corporate business objectives and current
FDA requirements. An annual Quality Report will be issued as a controlled document, is considered
confidential, and must not be copied, re-printed or the contents divulged to third-parties without the
explicit written authorization of the Quality Assurance department.

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2. DEFINITIONS
Annual Quality Report - A report issued annually by the Quality Assurance department which presents the
results of progress on quality-based initiatives within the company, and identifies additional opportunities for
continuous improvement.
Contract Review - The systematic activities carried out before signing the contract to ensure that
requirements for quality are adequately defined, free of ambiguity, documented and feasible by the supplier
or service provider.
Corrective Action - An action taken to eliminate the causes of an existing non-conformity, defect, or other
undesirable situation to prevent recurrence.
Deviation - Written authorization prior to production or before provision of a service to depart from specified
requirements for a specified quantity or for a specified time.
Management Review - A formal quality evaluation by top management of the status and adequacy of the
quality system in relation to quality policy and new objectives resulting from changing circumstances.
Preventative Action - An action taken to eliminate the causes of a potential non-conformity, defect, or other
undesirable situation to prevent occurrence.
Quality - The totality of features and characteristics of a product or service that bear on its ability to satisfy
stated or implied needs.
Quality Assurance - All those planned and systematic actions to be implemented and demonstrated to
provide adequate confidence that an entity will satisfy given requirements for quality.
Quality Control - Operational techniques and activities that are used to fulfill requirements for quality.
Quality Management Review Committee (Quality Council) - A committee comprised of senior
management, including representatives from Research & Development, Commercial Operations, Quality
Assurance Department and Company President to conduct a formal quality evaluation of the status and
adequacy of the quality system. The Quality Council meets on an as needed basis, and all meeting minutes
from Quality Council meetings are retained in the Quality Assurance department.
Quality Management - All activities of the overall management function that determine the quality policy,
objectives, and responsibilities, and implement them by means, such as quality planning, quality control,
quality assurance and quality improvement.
Quality Manual - A document stating the quality policy and describing the quality system of an organization.
Quality Plan - A document which defines specific quality practices, resources, and sequence of activities
relevant to a particular product, project or contract.
Quality Policy - The overall quality intentions and direction of an organization related to quality, as formally
expressed by top management.
Quality System - The organizational structure, responsibilities, procedures, processes and resources for
implementing quality management.

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Quality System Review - A formal evaluation by top management of the status and adequacy of the quality
system in relation to quality policy and new objectives resulting from changing circumstances.

3. MANAGEMENT RESPONSIBILITY
Senior management is responsible for establishing the leadership role for ensuring quality performance and
providing the required resources to all operating units and departments to achieve these established quality
performance standards.
Management with executive responsibility shall ensure that the quality policy is understood, implemented,
and maintained at all levels of the organization. Senior management with executive responsibility, as defined
under the membership of the Quality Management Committee (Quality Council), will review the suitability and
effectiveness of the quality system on an annual basis, at a minimum, to ensure that the quality objectives
and requirements of the Quality System Manual are met. This review will include:
Identification of weaknesses and deficiencies in the Quality System, including those identified as a
result of internal and external audits and investigations and consideration of possible improvement
Reporting of test data, customer complaints and resulting investigations to identify areas where
nonconformities can be reduced or prevented
Verification that Corrective and Preventive Action (CAPA) procedures are effective
Results of other quality improvement activities
Management Engagement & Oversight
Responsibility for effectiveness of the Quality System includes participation by all employees, including
management. The company has provided all members of the organization with the knowledge that quality is
the responsibility of every employee. With respect to product, process, and the quality system, all members
of the organization are responsible for, and authorized to:
Take action to prevent the occurrence of non-conformities
Identify and record problems
Recommend and implement solutions
All employees of the organization are authorized to propose changes to the quality system. This includes
changes to policies, guidelines, procedures and practices. The proposals are subject to specified reviews and
approvals. All members of the organization are strongly encouraged to suggest and implement improvement
ideas.
Research & Development Management and Commercial Operations Management
The Research & Development and Commercial Operations Management are responsible for:
Supporting quality objectives through the preparation, issuance, continuous review, revision,
identification of areas for procedure(s) consolidation and eventual retirement of SOPs and related
guidelines
Ensuring that all required personnel are aware and trained in the requirements of the established
Quality System, including SOPs and related guidelines
Ensuring that all third-party operations used for any or all of the conduct of clinical studies, non-clinical
studies and manufacturing operations adhere to the requirements of the Quality System, contractual
requirements, SOPs and guidelines

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Quality Management
The Quality Assurance department has the responsibility and authority to ensure that the quality system is
maintained by:
Assuring the implementation of procedures that are required based on regulatory agency expectations
and the Quality Manual
Ensuring that all required personnel are trained in the requirements of the Quality Manual, SOPs,
guidelines and policies
Monitoring the performance of company operations and third-party operations to assure conformance
to the requirements of the Quality Manual, as promulgated under established SOPs and working
practice guidelines
Overseeing the quality system and reporting regularly to management regarding any quality issues
Reviewing contracts and assuring that the requirements for quality are planned and documented
Analyzing and reporting on issues of product, process, service and system non-conformity, including
customer complaints
Verifying the implementation of CAPA
Ensuring adequate documentation is available for describing all aspects of the GXP compliance
requirements
Implementing a system for conducting internal quality system audits and evaluation of third-party
operations providing products or service
Coordinating training activities
Conducting an annual review of the quality system and reporting the findings of that annual review in a
Quality Annual Report
Quality Management, Research & Development Management and Commercial Operations Management
Joint Responsibilities
Quality Management is required to be organizationally independent of Research & Development and
Commercial Operations Management. However, these functions may share responsibilities in areas, such as:
Authorization of written procedures
Training
Approval and monitoring of third-party operations
Retention of records
Monitoring of compliance to GXP requirements
Investigation of quality problems

4. QUALITY COUNCIL
Management review of the established Quality System historically was conducted within the Quality
Council. The Quality Council is defined as a committee of senior management comprised of Research &
Development, Commercial Operations, Quality Assurance and Company President. The Quality Council
meets on a periodic basis, to review opportunities for improvement to the quality management system,
including the Quality Manual, and review and discuss quality problems within the organization and third-party
operations, review trending results and metrics of quality incidents, and agree to required actions to minimize
recurrence and ensure continuous improvement. Meeting minutes from all previous Quality Council meetings
are required to be recorded and are maintained in the Quality Assurance department files.

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Resource Management
Each department is responsible for identifying resource needs, including GXP training requirements for
personnel, to ensure that personnel performing activities for which they have responsibility and authority,
have been trained accordingly. Management is responsible for providing adequate, qualified resources.
Training records are maintained by the Human Resources department.
Quality Policy
The quality policy is designed to promote a quality culture within the organization. The quality policy will
ensure that regulatory requirements and the perceived quality needs of customers are met during the
development, manufacture, testing, distribution of clinical and commercial products, and conduct of nonclinical and clinical studies.
Quality is the key element in satisfying customer needs and expectations, in measuring company
performance. To achieve quality performance, a set of comprehensive quality standards have been
developed that will enable the company to meet or exceed governmental regulatory requirements.
The company strives to continuously improve its reputation for quality performance throughout its operations
and all activities. This is exhibited by the continuous training that employees receive in appropriate job skills,
GLP regulations, GCP regulations, and GMP regulations, procedures, guidelines and policies. In addition,
another attribute of the quality policy is a commitment towards continuous improvement in the evaluation of
projects and services, during and after execution for identifying opportunities for improvement.
Goals of the quality policy are met by the promotion and use of the quality systems, quality assessment tools,
and technologies designed to produce clinical and commercial products, design and execute non-clinical and
clinical studies that meet or exceed regulatory requirements, and meet business needs and development of
well-trained employees.
All employees have a responsibility for achieving these high quality expectations set forth in the Quality
Manual.
The company is committed to develop, manufacture and release safe, effective and high quality
pharmaceutical products that comply with applicable regulations and standards that meet identity, strength,
quality, purity, safety, stability and performance requirements. The companys commitment to quality is an
integral and measured part of every aspect of our operation.

5. QUALITY SYSTEM
General
The Quality System has been established, documented and maintained as a means of ensuring that products
and services conform to specified requirements. The Quality Manual is a documented overview of the Quality
System and serves as a reference in the implementation and maintenance of that system.

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The Quality System serves as a platform for continuous improvement within the organization, and is
designed to address the needs of three (3) main customers, including compliance requirements from
regulatory agencies, quality expectations of patients and healthcare providers and company shareholders.



















The structure of the documentation used to define the quality system includes four levels.

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The first level is the Quality Manual, which includes the Quality Policy.
The second level is the standard operating procedures, which define the detailed operational requirements of
the Quality System within the company.
The third level is the quality system procedural guidelines that support standard operating procedures.
The fourth level represents records and reports as documented evidence of compliance to established
written procedures.
Quality System Procedures
The company has documented and implemented procedures in accordance with the requirements of the
Quality Manual. The details of these procedures depend on the complexity of the work, as well as the skills
and training needed by personnel implementing the procedures.
Quality Planning
Requirements for quality are defined and documented in quality plans, internal and external audit plans,
product specifications, process and cleaning protocols, nonclinical study protocols, clinical protocols, case
report forms, quality agreements and contracts with service providers and suppliers. These documents are
reviewed before approval to ensure quality expectations will be satisfied.

6. CONTRACT REVIEW
Contracts are prepared and reviewed prior to final agreement with service providers and suppliers. A
potential subcontractor or supplier must submit appropriate background information relating to facilities,
equipment, capacity, dosage form requirements, regulatory inspection history and organizational structure to
enable an initial evaluation of their capability to undertake the work associated with the contract.
Contracts are prepared and reviewed prior to final agreement with the service provider or supplier. The
review assures that requirements are adequately defined and that appropriate capabilities will be available
to meet requirements. Where applicable, contracts are required to comply with 21 CFR 312.52: Transfer of
Obligations to a Contract Research Organization.
Amendments to contracts receive the same review process as original contracts. Any amendment is correctly
transferred to the responsible functional group(s). Contract review records are maintained in a designated
file. Under established procedures, contracts with third-parties also are required to include documentation
supporting the training, education and experience of the third-party provider personnel (21 CFR 211.34).
As required, a quality agreement may be established for critical Contract Research Organizations, vendors
and suppliers, in order to augment existing contractual arrangements which further define specific roles and
responsibilities for quality requirements between the company and third-party operations.

7. DESIGN CONTROL
Design control depends upon project scope, GXP functional area involved, and if a third-party operation
is used, the service provider or supplier contract requirements. Design reviews include the review of
clinical protocols, nonclinical protocols, and master batch production records, prior to execution. These
design reviews are conducted by functional area, as defined within the scope of SOPs, working practice
guidelines or policies, as well as the quality assurance department, to ensure quality is built into the study or
manufacturing process.
Procedures have been established and implemented to control and verify the design of contracts, quality

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agreements, protocols intended for non-clinical and clinical studies, master schedules for nonclinical studies,
master batch record review, development reports and process validation protocols. These documents are
reviewed to ensure that they are written in sufficient detail, so that scientific and compliance requirements are
met and serve as the plan for design and development activities. This includes identifying functional group
responsibilities and resources required for implementation.
The organizational interfaces between different functional groups involved in the design process includes
Research and Development; which includes Discovery, Toxicology (nonclinical safety assessment), Clinical,
Pharmacovigilance, Biometrics and Regulatory Affairs; and Corporate Operations which includes Contracts
Administration department, Project Management, Information Management, Information Technology,
Marketing, Finance, Human Resources, Manufacturing and Quality Assurance.
The design process includes significant information sought from and transmitted, in many cases, to thirdparty operations. Information is documented in various forms, such as study reports, batch records,
controlled notebooks, trial master files, case report forms, product or study transfer reports, computer
printouts, medical information, contracts, quality agreements and study design requirements for intended
outcome. Design progress and issues are transmitted and reviewed within functional groups and third-party
operations based on project scope and contract requirements.
Design Input
Design inputs are identified in study objectives, product specifications and contracts with third-party
operations. These design inputs include molecular modeling, new compound screening models, market
research, formulations development, development reports, product specifications, method development and
manufacturing equipment cleaning verification studies.
Early animal screening and initial acute non-clinical study requirements are reviewed to ensure that quality is
built into the longer term chronic studies where compliance issues or scientific design of the study is critical
for the data to be submitted to regulatory agencies. Design input factors for nonclinical studies include
controls for personnel, control of test articles, animal care, facilities and equipment, study design, study
conduct, reporting of results, storage and retrieval of data.
Exploratory Phase I and Phase II clinical studies for determining safety profile and dose ranging requirements
are used to ensure the optimum design characteristics are included in later confirmatory Phase III clinical
trials. Review of Phase I and II clinical trial information allows determination of any significant systematic
flaws before initiating Phase III clinical trials. These system-related deficiencies can be corrected by protocol
design changes, case report form changes and enhancements in monitoring and training prior to initiation
of Phase III clinical trials. All studies and clinical trial product are designed to meet required regulatory
compliance requirements and standards, standard operating procedure, policy and working practice guideline
requirements.
Risk analysis is a required element of design input to identify issues related to safety of a new chemical entity
undergoing non-clinical assessment and Phase I safety clinical trials.
Design Output
Design output is documented in terms that can be verified or validated against design input requirements.
The output of these design activities are case report forms, master and executed batch records, study
protocols, process validation protocols and reports, cleaning validation protocols and reports, identification
of new compounds for clinical safety evaluation, and adequate, well-controlled and closely monitored safety,
exploratory and confirmatory clinical studies. These documents are developed to meet the design input
requirements, and reference acceptance criteria and other information crucial to the process or product
design.

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Design Reviews
Periodic planned and documented reviews of the designed process are performed by representatives of the
responsible functional groups involved in the design stage. As required, an independent person is involved
in conducting a review of the design input and resulting output. This review can be performed by a qualified
third-party consultant. Formal documented reviews of the design include, but are not limited to, the conduct of
interim analysis of exploratory clinical studies, the contract review process for third-party operations involved
in performing portions or all of the work, as well as clinical study reports, executed batch records and product
release certificate of analysis, method validation reports, process validation reports, cleaning validation
reports and nonclinical draft and final reports. These reports require approval from the functional groups, as
defined in applicable SOPs.
Design Verification
As the design process proceeds, design verification is conducted and documented to ensure that design
output corresponds to design input, i.e., product specifications met, or clinical study protocol requirements
satisfied. Verification that design inputs meet design outputs is accomplished by design reviews. Executed
batch records are reviewed against master batch record requirements; clinical batch manufacture, stability
batch manufacture and production batches are verified as meeting requirements, by subjecting the developed
product to in-process testing, final release testing and stability testing requirements, and if deemed
acceptable, the issuance of a GMP Certificate of Compliance. Nonclinical and clinical studies are verified
as meeting design input requirements by Quality Assurance oversight by the issuance of a GLP Compliance
Statement and issuance of a GCP Audit Certificate, respectively. Analytical methodology development,
product specification development based on process capability, and completion of adequate and wellcontrolled pivotal Phase III clinical trials are examples of design verification.
Design Transfer
SOPs and related control documentation are used to ensure that non-clinical studies, clinical laboratory
methodology, bio-analytical methods, manufacturing process and quality control analytical methodology
transfers are approved and meet contractual and regulatory compliance requirements.
Design and Process Changes
Changes to designs are documented by change control procedures, note to file, or under revision logs or
amendments to control records, such as SOPs, clinical study protocols, non-clinical study protocols, product
monographs, analytical methods or batch records. Design changes are implemented as product or process
continuous improvements based on design reviews, risk analysis, customer complaints, or CAPA resulting
from quality investigations and audits.

8. DOCUMENT CONTROL
Written procedures continue to be used to control and maintain documentation. The magnitude of control
is dependent on the type of document. Procedures have been established and are maintained to control
all Quality System documentation. These procedures describe the requirements for development, review,
approval, maintenance and retirement of SOPs, working practice guidelines and policies. All documentation
is uniquely identified. Documents are reviewed and approved by authorized personnel prior to issue. SOPs
are reviewed and updated as necessary, and on a default biennial basis. Documents are reviewed for the
purpose of re-issue after changes have been made, or in some cases, as part of the retirement phase of
the controlled document. Information of the description of the change, reason for the change, and in some
cases, the impact of the change, is required to be included. Superseded document masters are retained and
archived according to record retention procedures.

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9. PURCHASING
Documented procedures are used to control and coordinate purchasing activities. Third-party operations who
conduct non-clinical, clinical and manufacturing services are responsible to source qualified materials and
services. Suppliers are initially approved by evaluation of their capability. Procedures are in place to ensure
third-party operations are evaluated for business, quality and regulatory requirements. Third-party operations
are evaluated and selected on the basis of their ability to meet sub-contracted activity requirements. The
extent of control exercised over third-party operations depends on the impact of the sub-contracted service
on the product or process and previously demonstrated capability and performance. Records are maintained
of vendor audits and performance. All critical approved suppliers and service providers are required to accept
and sign a contractual agreement that defines basic quality and regulatory issues, including right to audit,
notification of change to the customer and regulatory inspection notification.
Purchase orders are required to contain data clearly defining the product or service being requested,
including precise identification by code, and/or specification providing the title and specified requirements.
Dependent on the type of service or supplier, quality assurance will review and approve purchasing
documents for adequacy of the specified requirements or performance standard prior to release. Copies of all
purchasing documents are retained.
Verification of Purchased Product
Purchased product or services will be verified to assure contract obligations have been met. In some
cases, the product or service will be evaluated at the supplier or service provider site by periodic quality
assessments.

10. PRODUCT IDENTIFICATION AND TRACEABILITY

At third-party operations, documented procedures have been established and are implemented for identifying
materials from receipt to final product release and shipment or executed protocols, case report forms or
final study reports. All finished product is identified by a unique reference number. Products intended for
use in company sponsored studies or as marketed product, are released by the company as the study
sponsor, and assigned a unique quality disposition release number. Traceability records include purchase
orders, certificates of analysis, certificates of compliance, process control charts, records of environmental
conditions and shipping records. Clinical packaging third-party operations and distribution centers for
marketed products are required to maintain records of the manufacture and distribution of clinical supplies
and commercially distributed product, respectively.

11. PROCESS CONTROL

Third-party operations used by the company have procedures that ensure non-clinical or clinical protocol
execution or material production is planned and carried out under controlled conditions in order to prevent
nonconformities. Critical process parameters are required to be identified and controlled to ensure
performance specifications are met. Controlled conditions include the following:
Batch records to define production requirements that are established and implemented to assure that
products have the safety, identity, strength, quality and purity they are purported to have.
Production equipment is approved based on installation and operation qualification requirements.
Qualified personnel are used for process execution
Facilities are designed and have adequate capacity to ensure segregation of materials, study subjects
and animal cages, to minimize mix-ups and cross-contamination
Processes are controlled through a variety of approaches, activities and techniques. The process control

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system is designed to control information, material and operator input into the process; technology, tools and
equipment used, process environment, process performance and process output.
Process controls used in clinical studies include the use of clinical monitoring, protocol stopping rules and
requirements for determining and adequately recording endpoint safety and efficacy information. The control
and verification of source documentation are critical process parameters in the conduct of adequate and wellcontrolled clinical trials. The sampling and control of bio-samples at critical time points also comprise process
control during clinical studies. Criteria for in-process evaluation, recording of critical system outputs and final
testing are also required for process control. Equipment and utilities that are used during material production
or study protocol execution are required to have suitable documented procedures for set-up, cleaning,
qualification calibration and preventative maintenance. Where the results of processes cannot be fully verified
by subsequent inspection, processes are carried out by qualified operators and require control of collection
of process parameters to ensure specified requirements are met. Processes are qualified as required by
specified requirements and regulatory requirements.
Records of process and equipment qualification, and descriptions of clinical and non-clinical study areas are
maintained as specified by specific procedures. Monitoring and control of process parameters and in-process
and finished product or study characteristics are performed and recorded in batch records, clinical and nonclinical protocols and reports.

12. INSPECTION AND TESTING

Inspection and testing activities, including specified requirements and resulting records, are documented
in SOPs, working practice guidelines, policies, laboratory notebooks, batch records, case report forms,
monographs, protocols, clinical study reports and draft and final non-clinical study reports. Documented
procedures are used to control and coordinate this activity supported by quality records.
Inputs to creating inspection requirements include contract requirements, batch record and protocol
requirements. Inspections are carried out with prescribed documents using qualified equipment and trained
personnel. Inspections may be performed by quality control personnel, study directors, study monitors,
clinical monitors or quality assurance personnel. Deviations, variances, exceptions and Out-Of-Specification
(OOS) test results are investigated, root cause identified and used in justifying final inspection, testing results
and product or study disposition.
Inspection and testing records are documented on certificate of analysis, executed protocols and site
monitoring trip reports. Records, including the identity of the person(s) performing the inspection or testing,
are maintained on file.

13. CONTROL OF INSPECTION, MEASURING AND TEST EQUIPMENT

All inspection, measuring and test equipment used at third-party operations have suitable procedures for setup, operation, cleaning, qualification, calibration and preventative maintenance. Test equipment is qualified
by documented procedures. Test methods used for product testing, clinical sample analysis and non-clinical
sample analysis are validated in accordance with documented procedures, and ensure that the measurement
uncertainty is known and consistent with the required measurement capability. This also includes the
checking and periodic re-checking of test software.
All equipment used for inspection, measuring and testing is uniquely identified, including traceability to
equipment model, location and calibration and preventative maintenance frequency requirements. Inspection,
measuring and test equipment and methods are selected to satisfy precision and accuracy requirements.
Records of calibration status, methodology used and test results are maintained according to documented
procedures. When equipment is determined to be out- of-calibration, the validity of the previous test results

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using the identified out-of-calibration equipment are required to be investigated and reconciled.

14. INSPECTION AND TEST STATUS

Third-party operations inspection and test status of product is identified to ensure that only product that
has passed the required inspections and undergoes quality disposition as approved is used for intended
investigative studies or distributed as commercial product. All products are identified to indicate conformance
or non-conformance with regard to inspection and test results. Only product that has passed the required
inspections and tests are permitted for release. Only clinical study reports, and final study reports from nonclinical studies that have undergone final quality control and quality assurance inspection are considered
approved. After inspection and test status by the third-party operation, the final authority responsible for the
release and disposition of conforming product or study is the Quality Assurance department.

15. CONTROL OF NON-CONFORMING PRODUCT

Product that does not conform to requirements specified in product acceptance criteria, protocols and
batch records are prevented from unintended use. Documented procedures are used to describe how
nonconforming products are identified, documented, evaluated, segregated, dispositioned and notification
provided from third-party operations to the company. Investigations to identify root cause and subsequent
actions are performed using documented procedures. Investigations of non-conformances are documented
on investigation forms and approved by Quality Assurance. Each nonconforming product investigation report
is uniquely identified.
The responsibility for review of nonconforming product ultimately rests with the Quality Assurance
department. Quality Assurance has the authority for dispositioning nonconforming product. Documented
procedures are used to investigate and determine subsequent actions.
Disposition alternatives include:
Rework or reprocess in accordance with documented procedures and regulatory requirements.
Rework and reprocessed product is treated and tested identically to the product with additional testing
performed, including stability testing, as required to maintain control of the product and demonstrate
equivalence to normally processed product
Reject and potential use for equipment or process qualification activities

16. CORRECTIVE AND PREVENTATIVE ACTION

Documented procedures for conducting investigations and identifying CAPA are established and maintained.
Any CAPA is commensurate with the risks involved and the magnitude of the problem.
Procedures for corrective action include effective handling and investigation of product and process
nonconformities, serious adverse events, customer complaints, Quality System nonconformities and
deviations and exceptions to non-clinical and clinical studies. Documented procedures are used to conduct
investigations to determine if the root cause is process-related, personnel-related or equipment-related.
Corrective action plans are then developed, implemented and their effectiveness evaluated.
Procedures for preventative action are established to minimize occurrence of nonconformities. These
procedures produce information that is analyzed to detect and eliminate potential, as well as actual, causes
of nonconformities. This information includes audit results, inspection and test results and management
reviews.
Preventative action plans serve as the basis for continuous improvement within the organization.

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Customer complaints are classified into categories to allow for better tracking of trends and evaluating
improvement in specific areas. Every complaint is communicated to relevant functions within the organization.
Responses to customer complaints are developed by the responsible functional group and reviewed by the
Quality Assurance department CAPA is implemented and verified as effective.
Relevant information regarding problems, including details of actions taken, are submitted as part of the
management review process, and are included, for commercially distributed product, as part of the annual
product reviews.
Records of CAPA are tracked and trended, and also maintained within investigation reports, deviation and
exception reports, quality incident reports and memos to files.
CAPA related to safety and performance of the product is reviewed by the Regulatory Affairs department to
determine whether they involve any incidents that meet regulatory reporting criteria.

17. CONTROL OF QUALITY RECORDS

Procedures have been established and implemented for the identification, collection, indexing, access,
filing, storage, maintenance and disposition of quality records in the Information (Records) Management
department. These requirements are designed to allow records to be legible and retrievable, and prevent
damage and deterioration. These records are essential for accurately demonstrating conformance to
specified requirements and effective operation of the quality system.

18. INTERNAL QUALITY AUDITING

Documented procedures have been established and implemented for performing internal quality audits. The
audits verify whether quality activities and related results comply with planned arrangements. The audits
are planned and scheduled by the Quality Assurance department based on importance of the activity to be
audited. Audits are performed by individuals whose primary responsibilities are independent of the activities
being audited. Results of audits are recorded in audit reports or in investigation report forms, where there
is a directed internal audit conducted as a requirement of an investigation or verification of CAPA. Quality
Assurance is required to follow up, verify and record implementation and effectiveness of corrective action(s)
taken. Results of quality audits are used as an input to the management review process.

19. TRAINING
Documented procedures for identifying training needs, including training in specific job skills, procedure
training and continuous training in regulatory requirements have been established. Personnel who perform
assigned tasks within the operation are required to be qualified on the basis of education, training and/or
experience.
Personnel qualification files are maintained for each employee, and include at a minimum, a written and
approved job description, curriculum vitae, records of training attended and procedures reviewed.

20. RISK ASSESSMENT

The intent of a well-designed quality system is to ideally prevent, if not minimize, re-occurrence of
deficiencies in order to meet regulatory requirements. The objective is to mitigate risk by process design
intended to eliminate risk. The end user of a well-designed pharmaceutical-based quality system is the
patient and consumer.

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Risk management within the GXP operational areas include:

GLP: long-term non-clinical studies where protocol deviations, study design problems, contamination
issues requiring frequent quality surveillance to ensure problems are identified early and appropriate
corrective action implemented.
GCP: (1) selection of qualified principal investigators and clinical sites suitable to comply with protocol
defined study requirements, (2) conceiving well-designed studies that minimize protocol exceptions/
deviations/violations and (3) introduction of qualified personnel to implement processes grounded in
compliance, efficiency, and ethical foundations.
GMP: quality surveillance and manufacturing personnel present at the Contract Manufacturing
Organization (CMO) during critical process steps, such as process validation runs and cleaning
validation, as well as technology transfer from one CMO to another CMO.

21. STATISTICAL TECHNIQUES

Statistical techniques are used for a variety of activities, including inspection sampling at third-party
operations, process and method validation, process capability, environmental monitoring, and statistical
analysis plans used in the interpretation of executed clinical protocols and quality improvements.
Procedures have been established and implemented to define and control the application of statistical
technique. These include use of process capability calculations to ensure an established validated
manufacturing process routinely operates within defined specifications relative to process variability.

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TOPICS TO CHOOSE TO WRITE ON INCLUDE THE FOLLOWING:

! Conducting Effective
Computer Validations:
Effective Documentation
Requirements

! System Level Impact

Assessment for Computer
Systems and Software
Packages

! Software Validation

! Validation of CAPA
Effectiveness

! Defining User Requirement

Specifications
! SAP Validation
! Excel Spreadsheets:
Validated Use in a
Regulatory Environment
! Electronic Records
Management
! Risk Analysis
! Interpreting FDA
Regulations
! Data Integrity

! Computerized Laboratory
Systems
! Validation and Part 11
Compliance of Electronic
Document Management
Systems
! IQ, OQ and PQ
! Internal/Supplier Auditing
! Maintaining Computer
Systems in a Validated State
! Industry Best Practice

! ERP Validation

! Retirement of Computer
Systems

! Configuration Management/
Change Control

! Software Lifecycle
Development Cycle (SDLC)

! Qualifying Vendors/Vendor
Requirements

! Validation vs. Qualification

! Validation of Configurable
Off-The-Shelf (COTS)
Computer Systems
! Preparing For/Managing an
FDA inspection
! LIMS
! Validation of PLC Systems
! Network Qualification
! Equipment Qualification
! Validation and Use of MS
Access Databases
! Writing Effective Test
Scripts

! Disaster Recovery Planning

! Warning Letters
! Master Planning
! Computer Systems
Evaluations
! Validation in a Virtual
Environment
! Custom Application
Validation
! Revalidation
! Computerized Systems for
GCP, GLP
! Training

CALL FOR AUTHORS

There are a number of benefits
of being one of our published
authors:
Establishes Yourself as
an Industry Expert. By
demonstrating your expertise,
you move into a select group;
setting yourself apart from non
published colleagues.
Industry Best Practice. You
are playing a role in helping
advance the current state of
industry best practice. You are
making a difference.
Builds Credibility and Name
Recognition. Consulting and
speaking opportunities may
present themselves in the
future.
Tests Your Expertise Against
our Peer-Review Process.
How do you measure up? Can
you produce excellence?
Giving Back. You are sharing
your ideas with fellow industry
professionals.
Great Addition. In the event of
a job search, a great addition to
your resume.

For more information,

please contact Glenn Melvin,
Publisher at 561-795-2785 or
glenn@enkap.com