Q7 GOOD MANUFACTURING PRACTICE

GUIDELINE FOR ACTIVE

PHARMACEUTICAL INGREDIENTS
 OBJECIVE

• It provides guidance for the manufacturing of active pharmaceutical ingredient

(APIs) under an appropriate system for managing quality. It is also intended to
help ensure that APIs meet the quality and purity characteristics that they
represent.
• In this guidance, the term manufacturing is defined to include all operations of
receipt of materials, production, packaging, repackaging, labelling, relabeling,
quality control, release, storage and distribution of APIs and the related controls.
• The Guide as a whole does not cover safety aspects for the personnel engaged.
 QUALITY MANAGEMENT
PRINCIPLES

• Quality should be the responsibility of all persons involved in manufacturing.

• Each manufacturer should establish, document, and implement an effective system for managing quality that
involves the active participation of management and appropriate manufacturing personnel.
• The system for managing quality should encompass activities necessary to ensure confidence that the API will
meet its intended specifications for quality and purity. All quality related activities should be defined and
documented.
• There should be a quality unit(s) that is independent of production and that fulfills both quality assurance (QA)
and quality control (QC) responsibilities. This can be in the form of separate QA and QC units or a single
individual or group, depending upon the size and structure of the organization.
• The persons authorized to release API should be specified.
• All quality related activities should be recorded at the time they are performed.
• Any deviation from established procedures should be documented and explained. Critical deviations should be
investigated, and the investigation and its conclusions should be documented.
• No materials should be released or used before the satisfactory completion of evaluation by the quality unit.
 RESPONSIBILITIES OF THE QUALITY
UNIT(S)

• The quality unit(s) should be involved in all quality-related matters.

• - The quality unit(s) should review and approve all appropriate quality-
related documents.
• - The main responsibilities of the independent quality unit(s) should not be
delegated.
• - These responsibilities should be described in writing and should include,
but not necessarily be limited to:
•
• 1) Releasing or rejecting all APIs. Releasing or rejecting intermediates for use
outside the control of the manufacturing company.
• 2) Establishing a system to release or reject raw materials, intermediates,
packaging and labelling materials.
• 3) Reviewing completed batch production and laboratory control records of
critical process steps before release of the API for distribution.
• 4) Making sure that critical deviations are investigated and resolved.
• 5) Approving all specifications and master production instructions.
• 6) Approving all procedures impacting the quality of intermediates or APIs.
• 7) Making sure that internal audits (self-inspections) are performed.
• 8) Approving intermediate and API contract manufacturers.
• 9) Approving changes that potentially impact intermediate or API quality;
• 10) Reviewing and approving validation protocols and reports.
• 11) Making sure that quality related complaints are investigated and resolved;
• 12) Making sure that effective systems are used for maintaining and
calibrating critical equipment.
• 13) Making sure that materials are appropriately tested and the results are
reported.
• 14) Making sure that there is stability data to support retest or expiry dates and
storage conditions on APIs and/or intermediates where appropriate.
 RESPONSIBILITY FOR
PRODUCTION ACTIVITIES:
• The responsibilities for production activities in a manufacturing setting, likely
for pharmaceuticals or APIs (Active Pharmaceutical Ingredients).
• It emphasizes the need for written procedures and documentation for all steps,
including: * Creating and approving instructions for production.
• * Following those instructions to produce intermediates or APIs. * Reviewing
and signing off on batch records.
• * Handling deviations by reporting, evaluating, investigating (especially
critical ones), and recording conclusions.
• * Maintaining cleanliness and disinfection of facilities. * Maintaining
premises and equipment with proper records.
• Calibration & Maintenance: Ensures equipment is accurately calibrated and
the facility is properly maintained, with records kept.
• Validation & Change Control: Validation protocols and
reports are reviewed and approved, and any changes to
products, processes, or equipment are thoroughly evaluated.
• Qualification: New or modified facilities and equipment are
qualified to ensure they meet standards.
 INTERNAL AUDIT ( SELF INSPECTION)

• To verify compliance with the principles of GMP for APIs, regular internal
audits should be performed in accordance with an approved schedule.
• Audit findings and corrective actions should be documented and brought to
the attention of responsible management of the firm. Agreed corrective
actions should be completed in a timely and effective manner.
 PRODUCT QUALITY REVIEW

• Regular quality-reviews of APIs should be conducted with the objective of

verifying the consistency of the process. Such reviews should normally be
conducted and documented annually and should include at least the
following:
• 1. A review of critical in-process control and critical API test results
• 2. A review of all batches that failed to meet established specification.
• 3. A review of any changes carried out to the processes or analytical
methods;
• 4. A review of results of the stability monitoring program
• 5. A review of all quality-related returns, complaints and recalls
• 6. A review of adequacy of corrective actions
• The results of this review should be evaluated and an assessment made of
whether corrective action or any revalidation should be undertaken.
Reasons for such corrective action should be documented. Agreed
corrective actions should be completed in a timely and effective manner.
 PERSONAL QUALIFICATION

• There should be an adequate number of personnel qualified by appropriate

education, training and/or experience to perform and supervise the
manufacture of intermediates and APIs.The responsibilities of all personnel
engaged in the manufacture of intermediates and APIs should be specified in
writing.Training should be regularly conducted by qualified individuals and
should cover, at a minimum, the particular operations that the employee
performs and GMP as it relates to the employee's functions.Records of
training should be maintained. Training should be periodically assessed.
 PERSONAL HYGIENE

• Personnel HygienePersonnel should practice good sanitation and health

habits.Personnel should wear clean clothing suitable for the manufacturing
activity with which they are involved and this clothing should be changed
when appropriate.Additional protective apparel, such as head, face, hand,
and arm coverings, should be worn when necessary, to protect intermediates
and APIs from contamination.Personnel should avoid direct contact with
intermediates or API.Smoking, eating, drinking, chewing and the storage of
food should be restricted to certain designated areas separate from the
manufacturing areas.
 BUILDING AND FACILITIES

1.DESIGN AND CONSTRUCTION:

Facilities should be designed for easy cleaning, maintenance, and
operation to minimize contamination. (4.10)
Sufficient space must be provided to prevent mix-ups and
contamination. (4.11)
Protected equipment can be located outdoors. (4.12)
Material and personnel flow should prevent contamination. (4.13)
 CONTINUE…

• Defined areas should exist for material receipt, quarantine, sampling,

storage, production,
•
• packaging, and laboratory operations. (4.14)
•
• Adequate washing and toilet facilities should be separate but
accessible. (4.15)
•
• Laboratories should be separate from production areas unless process
integrity is maintained (4.1)
 2.UTILITIES(4.2)

Utilities affecting product quality should be monitored and

documented. (4.20)
• Proper ventilation, filtration, and exhaust systems should
prevent contamination. (4.21)
• Recirculated air should be controlled for contamination risks.
(4.22)
•
• Pipework should be identified and positioned to prevent
contamination. (4.23)
•
• Drains should be of adequate size with anti-backflow
mechanisms. (4.24)
 3.WATER(4.3)

Water must be suitable for API manufacturing. (4.30)

Process water should meet WHO potable water standards unless
otherwise justified. (4.31)
Stricter specifications may be required for API quality. (4.32)
Treated water processes must be validated and monitored. (4.33)
• Water used in final API processing for sterile products must be
monitored for microbial contamination (4.34)
 4.CONTAINMENT (4.4)

Dedicated production areas should be used for highly sensitizing

materials like penicillins. (4.40)
High-risk materials require dedicated areas unless validated
cleaning procedures are in place. (4.41)
Measures should prevent cross-contamination from personnel
and materials.(4.42)
• Highly toxic nonpharmaceuticals should not be handled in API
production areas. (4.43)