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Good Manufacturing Process

Inspection Team

A team of inspectors consists of at least 2 with one assigned as lead. Where necessary, a subject matter expert (SME) may be called upon to join from a roster of approved Specialists who are designated based on their qualification and competency. In like manner, 1 or 2 trainees/observers may be also included by the lead inspector.

Frequency

A risk-based approach is practiced to establish the frequency of inspection based on the intrinsic risk associated with the product and manufacturing process and compliance history of the manufacturer.

Manner of Inspection

Inspection can either be:

I. Announced Inspection

Establishments eligible for pre-notification should meet all of the following requirements:

  • No history of a product recall, product complaint, and OOS results from CSL for the last three (3) years;

II. Unannounced Inspection

Pre-notification is not given in the following instances:

  • if the establishment does not meet the criteria under announced inspection,
  • subject for investigation,
  • for special assignments; or
  • routine inspection for establishments with the high-risk level determined at the previous inspection

 

 

Inspection Process

An opening meeting is held at the beginning on an inspection where the lead inspector discusses the inspection agenda which covers the purpose, scope, standard to be used, duration of inspection, roles of each member of the team and the inspection process. Appropriate adjustments in the agenda can be made, as necessary.

The conduct of inspection will consist of document review, walkthrough, interview with people involved in the manufacturing. The team may either go in pair, as individuals or break into smaller groups, when the members are more than four, to be able to cover the manufacturing site. They will ask questions and will want to see evidence that will establish if the company is in compliance with relevant GMP standards. If a finding is noted, they may want to see additional evidence as requested.

At the end of the inspection, the team will discuss amongst themselves and consolidates the findings (deficiencies or observations for improvement) classifies deficiencies, prepares inspection report. A closeout meeting is conducted and the inspection report is presented to the manufacturer for discussion. Classification of deficiencies is based on FDA Circular No. 2019-003 Guidelines for the Classification of Deficiencies Observed During Inspection of Drug Manufacturers.

In case a critical deficiency is observed the lead inspector recommends appropriate actions to the manufacturer depending on the degree of harm to patients that the deficiency may cause. The lead inspector directs submission of a CARPA Plan and objective evidence of compliance as well as for deficiencies classified as major and others.

The lead inspector may decide to discontinue the inspection in cases where critical findings resulting from gross contamination, mix-up, fraud, and others as may be determined, are identified and/ or where there are unsettled disputes or disagreement between the inspector and staff or officer of the company.

Period of Inspection

The length of the inspection period will depend on the complexity of the manufacturing process/es the need/s to be covered. Generally, an inspection will take 1-5 working days.

Deliberation

Deliberation may be pursued prior to submission of the inspection report if there is any critical deficiency not identified in the list of deficiencies and/ or if there is a concern on the classified major deficiency after the conduct of the inspection.

  • The deliberation and action will be undertaken at FDA office.
  • Deliberation is performed with the members of the inspection team, an independent qualified inspector and a senior qualifies inspector.

The outcome of the deliberation will be communicated, through a fromal reponse, to the manufacturer.

Compliance Period

After inspection, the manufacturer is provided with a post-inspection letter containing the deficiencies during the inspection. The establishment is given two (2) submissions of the Corrective Action and Preventive Action (CAPA) plan for all deficiencies. The plan must incorporate details of the corrective actions (s) and preventive action (s), due dates for compliance.

The response should be clear and comprehensive with a reasonable timeline to resolve the concerns. It is considered their commitment and the lead inspector utilizes the response to determine if compliance has been met in a timely and effective manner. Once accepted, it is expected that actions are implemented as described. Any significant changes or delays to the implementation should be communicated with the Lead Inspector. Failure to implement actions to address deficiencies will be identified at the next re-inspection and may affect the manufacturer’s re-inspection frequency.

The responses are normally reviewed within 2 weeks of receipt and if accepted, a follow-up inspection may be scheduled, as necessary. Additional information may be requested to provide, evidence or provide clarification, if necessary. Any such request will be communicated to the manufacturer. Otherwise, the CAPA report is finalized and the inspector accomplishes the risk assessment form to establish the frequency of inspection.

The manufacturer is informed by letter that the inspection has been closed out and a copy of the final report will be made upon request.