Category: Drugs-GMP

Guidelines for The Classification of Deficiencies Observed During Inspection of Drug Manufacturers

FDA CIRCULAR NO. 2019-003

14 FEB 2019

Subject:  GUIDELINES FOR THE CLASSIFICATION OF DEFICIENCIES OBSERVED DURING INSPECTION OF DRUG MANUFACTURE

 

I.  RATIONALE 

 

Republic Act (RA) No. 3720, as amended by RA No. 9711, declared it a policy of the State to adopt, support, establish, institutionalize, improve and maintain structures, processes, mechanisms and initiatives that are aimed, directed and designed to help establish and maintain an effective health products regulatory system.  Pursuant to the foregoing policy, the State, through the Food and Drug Administration, must enhance its regulatory capacity and strengthen its capability with regard to the inspection, licensing and monitoring of establishments, and the registration and monitoring of health products, such as drug products and drug manufacturers, respectively.

Consequently, and in order to achieve the objective of RA No. 9711 of ensuring the FDA’s monitoring and regulatory coverage over, and providing coherence in FDA’s regulatory system for drug manufacturers and drug products, it is imperative that classification of deficiencies noted during inspection of drug manufacturers is consistent, and drug manufacturers are guided with manufacturing practices considered non-compliant to FDA-implemented rules/ standards in the manufacture of drug products.

Finally, in compliance with the declared policy of the State laid down in Republic Act No. 11032 or the Ease of Doing Business and Efficient Government Service Delivery Act of 2018 to promote integrity, accountability, establish effective practices, aimed at efficient turnaround of the delivery of government services and the prevention of graft and corruption in government, the FDA is committed to take appropriate measures to promote transparency.

Hence, this Circular is hereby issued.

 

II.  OBJECTIVE

 

This Circular is issued to have uniform understanding in the classification of the noted non-conformances during inspection of drug manufacturers and provide guidelines to the drug manufacturing inspectorate service of the FDA’s Field Regulatory Operations Office, as well as drug manufacturers for uniformity of regulatory understanding consistent with the provisions of RA No. 3720, as amended by RA No. 9711, RA No. 11032, and relevant national and international standards and policies.

 

III.  SCOPE 

 

These guidelines shall apply to all local and foreign drug Good Manufacturing Practice (GMP) inspection, drug GMP inspectorate, and establishments manufacturing drugs including: household remedy, medicinal gas, traditional and herbal medicines, non-sterile, sterile, vaccines and biologicals, radiopharmaceuticals, blood and blood products and active pharmaceutical ingredients for human and animal use.

 

IV.  GUIDELINES 

 

For uniformity, efficiency and transparency, non-conformances observed during inspections are classified based on the following definitions:

  1. Critical deficiency – a deficiency which has produced, or may lead to, a significant risk of producing either a product which is harmful to the human or veterinary patient, or a product which could result in a harmful residue in a food producing animal.

It also covers findings of the manufacturer’s or its agent’s commission of fraud, misrepresentation or falsification of products, records or data, or withhold any relevant data contrary to the provisions of law, rules and regulations or appropriate standards.

  1. Major deficiency–a deficiency which indicates a major deviation from the terms of the marketing authorization/ product registration, PIC/S Good Manufacturing Practice guide and other internationally accepted standard; or which indicates a failure to carry out satisfactory procedures for release of batches of drugs; or

a combination of several “other” deficiencies, none of which on their own may be major, but which may together represent a major deficiency and should be explained and reported as such; or repetitive deviation for two or more consecutive inspections.

  1. Othersa deficiency which cannot be classified as either critical or major, but which indicates a departure from good manufacturing practice. A deficiency may be “other” either because it is judged as minor, or because there is insufficient information to classify it as major or critical.

 

For reference a list of observations classified according to the above definitions is attached as Annex A. The list is non-exhaustive and other observations may be added, removed, or re-classified as appropriate, subject to notice to the concerned stakeholders.

 

Deficiencies with upward-arrow marked (↑) are elevated to the next higher level of deficiency for findings noted in a sterile facility.

 

In case of findings classified as critical deficiency (ies) the establishment is directed to initiate outright, any or all of the following:

  1. Temporarily stop production of affected product line/s and further importation (in case of foreign audit findings) and/or distribution;
  2. Undertake or cause company-initiated recall of affected batches following existing FDA rules and procedure for product recall;
  3. Address the deficiencies, including submission of CAPA plan and objective evidence of compliance, not later than thirty (30) calendar days reckoned on the day following the receipt of the inspection report.

**For foreign drug GMP inspections with drug products already available in the Philippine market, submission of CAPA plan and objective evidence does not apply, and non- issuance of appropriate authorization is imperative as per FDA Circular 2014-016.

 

Apart from the foregoing, critical findings may result in the FDA imposing subsequent regulatory action, including disapproval of application, suspension or revocation of the issued authorization.

 

In case of major and other deficiencies, the inspector is authorized to direct the establishment to address the deficiencies, including the submission of CAPA Plan and objective evidence of compliance, not later than forty-five (45) calendar days reckoned on the day following the receipt of the inspection report.

 

 V.  REPEALING AND SEPARABILITY CLAUSES

 

Any provisions of existing FDA-issued Circulars or Memoranda that are inconsistent with this Circular are hereby repealed, withdrawn and/or revoked accordingly.

If any provision of this Circular or application of such provision to any circumstances is held invalid, the validity of the remainder of the provisions hereof not affected shall continue to be in effect.

 

VI.  EFFECTIVITY

 

This Circular shall take effect immediately.

 

NELA CHARADE G. PUNO, RPh

Director General

 

ATTACHMENTS:

Authority for the officers of Drug Good Manufacturing Practice (GMP) Inspectorate Task Force to conduct inspection and post marketing surveillance in accordance with Republic Act 9711, even beyond office hours, as the need arises in Luzon, Visayas and Mindanao from January to December 2019

FDA PERSONNEL ORDER
No. 2019-0020


SUBJECT: Authority for the officers of Drug Good Manufacturing Practice (GMP) Inspectorate Task Force to conduct inspection and post marketing surveillance in accordance with Republic Act 9711, even beyond office hours, as the need arises in Luzon, Visayas and Mindanao from January to December 2019

 

In enforcing Republic Act No. 3720 as amended by Republic Act No. 9711 and its implementing Rules and Regulations, the Drug GMP Inspectors under the task force created per FDA Order 2018-085 and FPO 2018-0820 are hereby authorized and empowered, among others, to:

 

1) assume primary jurisdiction in inspecting and evaluating domestic or foreign drug manufacturers;
2) monitor, inspect and evaluate drug products and establishments covered by the FDA Act of 2009, its Rules and Regulations, and other relevant laws, for the purpose of the issuance of the necessary authorizations;
3) collect samples of drug products including finished or unfinished materials, containers, and labelling;
4) recommend for issuance of appropriate authorizations or disapproval of an application for a License to Operate or other-related authorization;
5) issue Certificates of Compliance with technical requirements to serve as basis for the issuance of appropriate authorization and spot check for compliance with regulations regarding operation of drug manufacturers;
6) conduct post marketing surveillance of all drug products;
To submit a report to serve as basis for the motu proprio action of the Deputy Director-General for Field Regulatory Operations Office, upon finding, in the course of its evaluation, monitoring, inspection and spot checking, of any non-compliance and violation of other requirements required by the FDA, its implemented laws, Rules and Regulations;
7) To exercise such other powers and perform such other GMP-related functions that may be assigned or necessary to carry out the above duties and responsibilities.

 

To carry out the above functions, powers and duties, the duly designated officers or employees FDA are authorized by the above law to (1) enter, at reasonable hours, any factory, warehouse, or establishment in which drug products are manufactured and/ or held for introduction to the market; and (2) inspect in a reasonable manner, such factory, warehouse, establishment, and all pertinent, finished or unfinished materials, containers, and labelling therein. Such inspection would necessarily include collection of sample, examination of documents relevant to the manufacture of drug products to aid in assessing safety, efficacy, purity, and quality of drug products, and taking copies of documents, pictures, and voice or video recording, whenever necessary, as objective evidence.

 

Pursuant to the above powers, functions, duties, and in the interest of the service, the following Food-Drug Regulation Officers of FROO are hereby authorized and mandated to implement the above functions, duties, and powers over drug manufacturers and drug products, even beyond office hours, as the need arises within Luzon, Visayas and Mindanao. The Licensing Officers may be allowed to perform the above functions subject to the approval of the Deputy Director General of FROO, as the need arises. The foregoing authority shall be valid from 15 January to 15 December 2019:

 

Name

Office

1.      Pia Rose A. Belarmino RFO-NCR
2.      Angeli B. Casala RFO-NCR
3.      Carolyn P. Custodio RFO-NCR
4.      Frances Glorie D. De Luna RFO-NCR
5.      Marissa C. Fajardo RFO-NCR
6.      Mary Angeline V. Francisco RFO-NCR
7.      Michael E. Galang RFO-NCR
8.      Lelian B. Indac RFO-NCR
9.      Jackerwin R. Maur RFO-NCR
10.  Clarissa A. Mendoza RFO-NCR
11.  Cristy Hanna V. Mendoza RFO-NCR
12.  Ma. Lynn Rachelle A. Natividad RFO-NCR
13.  Rioriza A. Ortilano RFO-NCR
14.  Don Bryan A. Orendain RFO-NCR
15.  Raymond L. Sia RFO-NCR
16.  Ma. Suzette R. Sta. Clara RFO-NCR
17.  Rowena K. Velasco RFO-NCR
18.  Maria Lolita B. Abo-ol RFO-NCR
19.  Evadine Astrid M. Pera RFO-I
20.  Janelle L. Lim RFO-II
21.  Mary Christine C. An RFO-V
22.  Edwin E. Castillo, Jr. RFO-V
23.  Ma. Lexia T. Jancorda RFO-VI
24.  Ma. Salome R. Largo RFO-VII
25.  Irish B. Samar RFO-VII
26.  Benczint Benedikt C. Ortega RFO-VIII
27.  Keith Bryan Vincent R. Angeles RFO-IX
28.  Lorelie Joy A. Acha RFO-X
29.  Eba Marie Antonette W. Inis RFO-XI
30.  Mayen P. Abdullah RFO-XII
31.  Lucille Glenda T. Bug-os RFO-XIII

 

Under this Order, these personnel are entitled to avail compensatory time off pursuant to CSC-DBM Joint Circular No. 2 dated 04 October 2004 for services rendered during Saturdays, Sundays and/ or holidays in lieu of overtime pay, provided that they have not incurred any absences tardiness, or undertime during the week (five working days) immediately preceding the weekend and/or holiday they rendered service.

 

Airfare, transportation expenses, van rental, per diem (above 50 kilometres radius from official station), actual and other incidental expenses of the mentioned officers, including accommodation shall be charged against the respective Regional Field Offices funds subject to the usual accounting and auditing rules and regulations.

 

ATTY. EMILIO L. POLIG, JR.
OIC, Deputy Director General
Field Regulatory Operations Office

ATTACHMENTS:

/ In Drugs-GMP / By Mark Alcantara / Comments Off on Authority for the officers of Drug Good Manufacturing Practice (GMP) Inspectorate Task Force to conduct inspection and post marketing surveillance in accordance with Republic Act 9711, even beyond office hours, as the need arises in Luzon, Visayas and Mindanao from January to December 2019

Notice on the Adoption of the PIC/S Guide to GMP

Administrative Order (AO) No. 2012-008, or the rules on the “Adoption and Implementation of the Pharmaceutical Inspection Cooperation Scheme (PIC/S) Guide for Good Manufacturing Practice (GMP) for Medicinal Products”, directs all drug establishments to adopt the current version of PIC/S GMP Guide as the standard for Good Manufacturing Practice.

 

The AO likewise orders that all supplements and revisions related to the PIC/S GMP Guides shall be adopted automatically.

 

Notwithstanding, it is reiterated that the version of the PIC/S Guide to GMP being implemented at this juncture is PE009-13, which took effect on 1 January 2017, until further notice from FDA.

Creation of Technical Working Group for the Effective Implementation of the PICS/GMP Guide for Medicinal Products

FDA MEMORANDUM CIRCULAR NO. 2018-003

13 July 2018

TO : All Drug Establishments and concerned Offices, Officers, and Personnel within Food and Drug Administration

SUBJECT : Creation of Technical Working Group for the Effective Implementation of the PICS/GMP Guider for Medicinal Products

 

The Pharmaceutical Inspection Cooperation Scheme (PIC/S) Good Manufacturing Guide for Medicinal Products was officially adopted and implemented by virtue of the issuance of Administrative Order No. 2012-008 dated 25 June 2012. For capability building purposes, Paragraph 5, Item VI of the Administrative Order specifically authorizes the FDA and industry to provide trainings and workshops and may create technical working group/s for the effective implementation of the PIC/S Guide.

 

Hence, a Technical Working is hereby established composed of the following:

 

  1. FIELD REGULATORY OPERATIONS OFFICE, as Lead
  2. CENTER FOR DRUG REGULATION AND RESEARCH, as Co-Lead
  3. Two representatives from the industry representing local manufacturers and distributors (importers).

 

The TWG shall perform the following:

 

  1. Undertake impact analysis concerning the implementation of the PIC/S guides or requirements and recommend to FDA and industry appropriate actions;
  2. Coordinate with the FDA and industry for the provision of trainings, workshops, dissemination of information to stakeholders, and other appropriate action for the smooth implementation of the PIC/S guides or requirements including supplements or revisions thereto;

 

All materials, food, transportation, equipment, and other financial requirements that may be needed by the TWG during meetings shall be sourced out from available funds of the FDA, subject to the usual accounting and auditing rules and regulations.

 

This Order shall take effect immediately and shall be valid until revoked.

 

NELA CHARADE G. PUNO, RPh

Director-General

 

ATTACHMENTS:

Authority of FDA Inspectors

FDA Circular 2012-011

 

05 September 2012

 

TO: ALL FDA Inspectors and Drug Establishments

 

SUBJECT: Authority of FDA Inspectors

 

Pursuant to Republic Act 9711 and its implementing rules and regulations, the Food and Drug Administration was tasked to safeguard public health. Article II section c stipulates that the FDA has the function “to analyze, test and/ or inspect health products in connection with the implementation of the FDA Act of 2009, these Rules and Regulations, other relevant laws, and FDA-promulgated issuances; In line with this Food-Drug Regulation Officer (FDRO) is hereby authorized:

 

  1. To enter, at reasonable hours, any factory, warehouse, or establishment in which drug products are manufactured, processed, packed, or held, for introduction into domestic commerce, or are held after such introduction, or to enter any vehicle used to transport or hold such health products in domestic commerce;
  2. To inspect, in a reasonable manner, such factory, warehouse, establishment, or vehicle and all pertinent equipment, finished or unfinished materials, containers, and labelling therein;
  3. To take pictures and copies of documents within the premises, as necessary;
  4. To inspect, to open and examine any receptacle or package that contains drug products, as necessary;
  5. To collect samples of health products. After which, a receipt describing the samples obtained shall be issued to the person-in-charge of the premises/ establishment inspected.
  6. To implement orders of seizure, to seize and hold in custody any article or articles of any drug, in-vitro diagnostic reagents, biologicals, and vaccine that is adulterated or misbranded, when introduced into domestic commerce pending the authorized hearing under the FDA Act of 2009, these Rules and Regulations, and as far as applicable, other relevant laws. This will be based on scope of authority unless otherwise assigned.
  7. To exercise such other powers and perform such other functions as may be assigned or necessary to carry out its duties and responsibilities. All FDA Inspectors shall be issued a certificate of authority which may be presented to the company during the inspection or investigation.”

 

Furthermore, the company must fully cooperate in the inspection and not to obstruct the inspector during inspection process. Violation of such shall be dealt with existing penalties as per Republic Act 9711 and its implementing rules and regulations.

 

REPEALING CLAUSE

All other issuances inconsistent with this Circular are hereby repealed.

 

SEPARABILITY CLAUSE

In case any provision of this Circular is declared contrary to law or unconstitutional, other provisions which are not affected hereby remain in force and in effect.

 

EFFECTIVITY

This Circular shall take effect immediately.

 

NICOLAS B. LUTERO III, Esq., CESO III

Assistant Secretary

Officer-in-Charge, Food and Drug Administration

 

ATTACHMENTS: