Overview of Dietary Supplement GMP Inspection Trends Quality Session 6

Transcription

1 Overview of Dietary Supplement GMP Inspection Trends Quality Session 6 Presented by: Dean R. Cirotta, MBA President & Chief Operating Officer EAS Consulting Group, LLC 1700 Diagonal Road, Suite 750 Alexandria, Virginia dcirotta@easconsultinggroup.com 21 CFR Subparts A General Provisions B Personnel C Physical Plant and Grounds D Equipment and Utensils E Requirement to Establish a Production and Process Control System F Quality Control G Components, Packaging, and Labels and for Product That You Receive for Packaging or Labeling as a Dietary Supplement H Master Manufacturing Record I Batch Production Record J Laboratory Operations K Manufacturing Operations L Packaging and Labeling Operations M Holding and Distributing N Returned Dietary Supplements O Product Complaints P Records and Recordkeeping 2 1

2 Who is subject to the regulation? (111.1) You are if you Manufacture Package Label Hold Distribute (own label distributor) A dietary supplement There are a few exclusions in 111.1(b) for example: Retailers Dietary Ingredient Suppliers Component Suppliers 3 Compliance Policy Guide for Dietary Supplements: Dietary Supplements - Import And Domestic (Implementation date 03/26/2010) GMP Violations Under section 402(g)(1) of the Federal Food, Drug and Cosmetic Act (the Act), a dietary supplement is adulterated if it has been prepared, packed, or held under conditions that do not meet current good manufacturing practice regulations. Major deviations from cgmps include: Lack of master manufacturing records or significant requirements not included; Lack of finished product release criteria or failure to test (all or subset of finished batches) or meet finished product release criteria critical to product safety and quality; For significant dietary ingredients, e.g. those that make up the bulk of the product, failure to establish specifications for incoming material or failure to conduct identity testing; No quality control review procedures or significant quality control procedures not implemented; No batch records; Significant physical plant deficiencies. Districts should prepare and submit to CFSAN/Division of Enforcement (DE)/Labeling Compliance Team (LCT) a Warning Letter recommendation for any firm with any of the above deviations EAS Consulting Group, LLC. 4 2

3 Commonly Cited Deficiencies In Did not address your quality control operations responsibilities for (---many---) Insufficient qualifications of QC personnel Lack of, or inadequate, QC procedures Failure to perform material reviews or performed inadequately Lack of adequate QC involvement in product dispositions Failed to test all (or sub-set) of finished batches 5 Commonly Cited Deficiencies In No specifications for identity, purity, strength and composition for each component. No specification for any point, step, or stage in the manufacturing process where control is necessary. No specifications for identity, purity, strength and composition of your finished DS products and limits of potential contaminants. Failure to formulate to 100% of label claim. Inadequate sampling procedures & practices. 6 3

4 Commonly Cited Deficiencies In No specifications for products received for packaging, labeling and distribution to assure they are properly identified and consistent with the PO. Failed to conduct at least one appropriate test or examination to verify the identity of each dietary ingredient. You relied on COAs. Inadequate supplier qualification program & procedures. Failed to establish master manufacturing records (MMRs) for each formulation and batch size that you manufacture meeting the requirements of 21 CFR 205 & Commonly Cited Deficiencies In Failed to create a master packaging record (MMR/MPR) for packaging and labeling operations. Your batch production records (BPRs) did not include complete information relating to the production and control of each batch as required by 21 CFR 255 & 260. Lack of adequate documentation demonstrating appropriate training was provided. List of required training for all personnel Training conducted (CGMP, SOPs, job skills) Documentation of training effectiveness/employee qualification 8 4

5 Commonly Cited Deficiencies In Insufficient and/or inadequate SOPs. No written procedures covering returned products. No written procedures covering product complaints. Failed to manage, document & investigate product complaints. Failed to make and keep records of product distribution. Failed to collect and hold reserve samples or each lot of packaged product. No product stability data supporting expiration dating. 9 Commonly Cited Deficiencies In Significant plant facilities deficiencies: Inadequate cleaning & sanitizing practices Insufficient water monitoring and controls Inadequate formal equipment preventive maintenance and calibration programs Failed to hold components and products under appropriate conditions of temperature, humidity and light so the (their quality) is not negatively affected. Failure to maintain records for Adverse Events and report Serious Adverse Events. 10 5

6 Top Violations of 21 CFR 111 Dietary Supplement Adulteration Comments by Daniel S. Fabricant, Ph.D. Director, Division of Dietary Supplements USP Economically-Motivated Adulteration of Food Ingredients and Dietary Supplements, Rockville, MD September 25th, Dietary Ingredient Testing 2. Finished Product Specs 3. Finished Product Testing 4. Product Complaints 5. QC Procedures 6. Qualifying Supplier C of As 7. MMRs 8. Incomplete BPRs 9. Holding and Distribution Records 10. Holding and Distribution SOPs 11. Dietary Ingredient Specs 12. Returned Product SOPs 13. No Reserve Samples 11 FDA Inspection Update First inspections of dietary supplement companies began in Summer inspections conducted in inspections conducted in inspections conducted in inspections as of Sept inspections through Q (Oct Dec 2013) Warning Letters 8 issued in issued in issued in issued as of

7 Warning Letters Most warning letters are being issued: after the firm has had an opportunity to provide responses to their 483 observations approximately 4-7 months following the actual FDA inspections Many warning letters indicate an inadequate 483 response from the firm; The responses are too general and not focused The response does not address the systemic or global issue, just the specific observation The corrective actions do not address the actual root-cause The firm does not consider other products that may be affected by the same observation No evidence or documentation is provided to substantiate the corrective actions 13 FDA Perspectives The agency is out of patience as they are still see warning letters to companies for not doing the most fundamental things. Inspections will increase, will become more stringent and will go deeper. Reviews will become more technical in the scope of specifications, procedures and laboratory controls. Expect more warning letters and escalating enforcement actions. Increased focus on tainted supplements. 14 7

8 In Conclusion Dietary supplement companies should be educating themselves so they can identify and address all of the major violations in their facilities Thoroughly understand 21 CFR Part 111 requirements and the Preamble Train all employees on GMPs Read Warning Letters and Inspection Reports Familiarize yourself with FDA s Compliance Program Stay up to date on related legislative activity and get involved Finally, companies, regardless of size, need to understand that it has been almost 7 years since the publication of Final Rule: June 25, 2007 and the FDA is taking a very firm and aggressive stance regarding dietary supplement GMP violations and they need to act quickly and effectively to ensure their compliance with the dietary supplement GMPs. 15 Thank You 8