Implementation of GMP’s for Cosmetics in a Changing Global

Environment Presented to the

New England Chapter

Society of Cosmetic Chemists

April 5, 2012

by

Joseph Albanese

3V, Inc.

and

Karl F. Popp, R. Ph.

KPOPP Consulting, LLC

Course Goals• Provide an Overview of US, EU, and ASEAN GMP

Regulations affecting Cosmetics• Discuss Quality Systems• Review Procedures for Writing, Issuance,

maintenance and Implementation of SOPs• Show How GMPs affect Product Processing

– Raw Materials– Manufacturing and Packaging Batch Records– Equipment Cleaning Labeling and Storage– QC Testing

• Managing Water Systems• Auditing for Compliance• Introduce Process and Cleaning Validation

Why are there GMPs?• Responsibilities

– Corporate– Personal– Legal

• FDA• European Regulations• Association of Southeast Asian Nations• Importation• Export• Fraud• SOMEONE GOT HURT !

Short Story on GMPs

• Prevent contamination• Prevent mix ups and errors• Instill process controls• Insure product quality• Save everyone money

S A F E T Y

Basic Rule of Thumb

• Whether imported, exported or made within the country, cosmetics MUST be in compliance with the provisions of the regulations of the country of sales, and may also need to be in compliance with the regulations with the country of manufacture.

Cosmetic GMP Regulations• US Cosmetic GMPs

– FD&C Act [Sec. 301] prohibits introduction, or delivery for introduction, into interstate commerce cosmetics that are

• adulterated [Sec. 601], or• misbranded [Sec. 602].

– FDA has authority to inspect firms, establishment, equipment, unfinished and finished materials, containers and labeling [Sec. 704]

Cosmetic GMP Regulations• EU Cosmetic GMPs• Guidelines aimed at cosmetics manufacturers in

order to improve safety, offer organisational and practical advice on the management of the human, technical and administrative factors affecting product quality.

• Describe the manufacturing conditions and management activities involved in the different stages of production, from the purchase of the raw materials to the dispatch of the packaged end-products.

• Current Requirement Reference: ISO 22716

European Cosmetic Directive• Article 5.1 “Good Manufacturing Practice” requires that

“Manufacturing of cosmetic products shall comply with good manufacturing practice…..”

• Article 5.2. states that “Compliance to good manufacturing practice shall be presumed where manufacturing is in accordance with the relevant harmonized standard,…..”

• The ISO standard 22716 (2007) ”Cosmetics – Good Manufacturing Practices (GMP) – Guidelines on Good Manufacturing Practices” has been approved an published in 2007 and is becoming more and more accepted at international level.

• It is expected that this standard will become a harmonized standard soon after the publication of the new cosmetic regulation (2013)

• Therefore compliance to this standard will guarantee compliance to Article 5 of the cosmetic regulation.

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Cosmetic GMP Regulations• ASEAN Cosmetic GMPs

– Driven by Article 8.1.c [ASEAN Cosmetic Directive]

• Follows primarily EU activities• Guidelines intended as a general guideline for the

manufacturers to develop its own internal quality management system and procedures

• Goal:– “The final products must meet the quality

standards appropriate to their intended use to insure consumer’s health and benefit”

What do the “Guidelines Cover”Comparison of Regulations US EU ASEAN Topic Introduction X X X Quality System X X X Personnel X X X Training X X X Premises X X X Equipment X X X Sanitation/Hygiene X X X Production/Manufacturing X X X Purchasing X Quality Management X Quality Control X X X Documentation X X X Out of Spec Result Handling X Labeling X X Internal Audits X X Storage X X Contract Manufacturing and Analysis

X X

Complaints X X Subcontracted Manufacturing X Sample Retention X X Recalls X Shipping Traceability X Glossary X X

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Comparison of GMPSUS FDA, WHO & EU

• Responsibility for Quality– FDA – the QC unit is responsible for quality – WHO & EU – define both separate and joint responsibilities

for the QC unit and production management

• Personnel Qualifications– FDA – education, knowledge, skills or experience needed

for specific job functions are not defined– WHO & EU – provide such definitions & requirements

• Production & Process Controls– FDA – focuses on levels of approval– ICH – focuses on stability requirements

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HarmonizationInternational Cooperation on Cosmetic Regulation

(US, European Union, Canada, Japan)

• Good manufacturing practices• Ingredient labeling / INCI names• Nanotechnology• Market surveillance• Authorized substances• Animal testing and alternative methods• Sunscreen regulations and test methods

Definition of cGMP

“The minimum current good manufacturing practice for methods to be used in, and the facilities or controls to be used for, the manufacture, processing, packing or holding of a drug to assure that such drug meets the

requirements of the act as to safety, and has the identity and strength and meets the quality and

purity characteristics that it purports or is represented to possess.”

- Title 21 Code of Federal Regulations (CFR), Part 210.1

What is “current” and “good”?• Feasible for manufacturers to implement

• Not just for DRUGS

• Contributes to ensuring the safety, quality, or purity of the drug product

• The value of the contribution exceeds the cost or other burdens of implementation

• It does not have to be the most prevalent practice in the industry

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Does it apply to cosmetics too?

Yes, cosmetics too.

“These regulations clearly apply to all drugs whether or not they are characterized as old drugs, new drugs, investigational drugs, or ingredients of drugs, devices or cosmetics.”

SOURCE: Good Manufacturing Practices for Pharmaceuticals 4th Ed, Willig & Stoker, Preface pp III-IV.

Sidney H. Willig - Drug Law Unit Temple UniversityJames R. Stoker - Legal Dept. Sterling Drug

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FDA Definitions• Cosmetics - cleanse and beautify the body; not including

soaps (alkali salts of fatty acids). DO NOT REQUIRE PRE-MARKET APPROVAL BY THE FDA.However, color additives must be preapproved!

• Drugs – alter the structure or function of the body. Intended to diagnose, treat, care, mitigate or prevent disease.DO REQUIRE PRE-MARKET APPROVAL BY THE FDA.

• Both – a.k.a. “OTC Drugs” shampoos that are also antidandruff, deodorants that are also antiperspirants, dentifrice with fluoride, creams & lotions with sunscreens, antibacterial cleansers

OTC Drug vs. CosmeticOTC Drug• Pre-market approval or

USP monograph required• Safety & efficacy must be

cleared• Subject to cGMP• Must not be adulterated

or misbranded• Establishments &

products must be registered

• No prescription required• Symptom relief

Cosmetic• Pre-market approval not

required• No pre-market clearance of

product or ingredient claims, safety or efficacy

• Must not be adulterated or misbranded

• Establishment & product registration not mandatory

• No prescription required• Adverse event reporting is

not required (yet)• Cleansing, beautifying, or

altering the appearance

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FDA Focus• Office of Cosmetics & Colors (OCAC) / Center for

Food Safety and Nutrition (CFSAN) (Dec 6, 2006)– Microbial contamination– Illegal color additive use– Bovine Spongiform Encephalopathy (BSE)– Bioterrorism/Counterterrorism (BT/CT)

• Center for Drug Evaluation & Research (CDER)– Dermatology– OTC Products– Compliance

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FDA Cosmetics Mission Statement

“ . . . Protect the public health by

ensuring that cosmetics are

safe and properly labeled . . .”

- Food and Drug Administration Modernization Act (FDAMA) of 1997, Sec. 406(b)(2)(D)

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The Focus of the FDA’s cGMPs

- Annual Product Reviews

- Consumer Complaint Reviews

- OOS / Failure Investigations

- Change Control

- Continuous Improvement

- Reprocessing

- Salvage / Returns

- Rejects

- Stability Failures

- Quarantined Products

- Validation

- Training / Qualification of Employees

You’re not likely to fly under the radar screen

• “Interstate commerce” means between any State, Territory or the District of Columbia. It applies to all steps in a product's manufacture, packaging, and distribution.

• “Commercial distribution” means annual gross sales in excess of $1,000 for that product.

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Cosmetic Safety, as per the FDA• Can not contain any of the restricted ingredients.

• Cosmetic firms must substantiate the safety of their products before marketing them.

• If safety is not substantiated the following warning must be on the label or the product is misbranded:– WARNING- The safety of this product has not

been determined.

• Product recalls of hazardous cosmetics is voluntary.– FDA works with the courts to remove adulterated

and/or misbranded cosmetics from the market– Restraining orders, product seizure, criminal

prosecution of firms and individuals are all possible.

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Title 21, CFR for Cosmetic Products• 21 CFR PART 1 - General enforcement regulations• 21 CFR Part 2 - General administrative rulings & decisions• 21 CFR Part 20 - Public Information• 21 CFR Part 250 - Requirements for drugs & cosmetics• 21 CFR SUBCHAPTER G – COSMETICS• 21 CFR PART 700 – GENERAL Subpart A – General Provisions

Subpart B – Requirements for Specific Cosmetic Products• 21 CFR PART 701 – COSMETIC LABELING,

Subpart A – General ProvisionsSubpart B – PackagingSubpart C – Labeling of specific ingredients

• 21 CFR PART 710 – Voluntary registration of cosmetic product establishments

• 21 CFR PART 720 Voluntary filing of cosmetic product ingredients & cosmetic raw material composition statements

• 21 CFR PART 740 – Cosmetic Product Warning Statements• 21 CFR PART 820 – Quality Systems regulations

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Adulterated (Sec. 601)• Injurious to users under conditions of customary use

because it contains, or its container is composed of, a potentially harmful substance, chemical contaminant or prohibited ingredient

• It contains filth and/or pathogenic bacteria

• It contains a non-permitted or in some instance non-certified, color additive

• It is manufactured or held under unsanitary conditions whereby it may have become injurious to users or contaminated by filth

Prohibited Cosmetic Ingredients 1. Hexachlorophene (21 CFR 250.250) 2. Mercury Compounds (21 CFR 700.13) 3. Chlorofluorocarbon Propellants (21 CFR 700.23 and

2.125) 5. Acetyl ethyl tetramethyl tetralin (AETT) 6. 6-Methylcoumarin (6-MC) 7. Musk Ambrette 8. Nitrosamines 9. Dioxane10. Certain cattle materials

Organic dyes or pigments require pre-market approval and must be certified by the FDA before use.

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Misbranded (Sec. 602)• Failure to comply with the Fair Packaging & Labeling Act

of 1967

• Failure to comply with the Poison Prevention Packaging Act of 1970

• Failure to state prominently and conspicuously any information required by the FD&C Act

• False or misleading labeling

• Misleading container presentation or fill

Restricted Cosmetic Ingredients(permissible as unintentional contaminants)

1. Bithionol

2. Halogenated Salicylanilides

3. Chloroform

4. Vinyl chloride

5. Zirconium containing complexes in aerosol cosmetic products

6. Methylene chloride

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Other FDA positions . . .• Natural

– Not defined in FD&C Act or in FDA regulations for cosmetics

– May be defined for other commodities as ‘minimal processing’, ‘semi-synthetic’, ‘nature-identical’, etc.

• Organic– Not defined in FD&C Act or in FDA regulations for

cosmetics– Defined by USDA for agricultural commodities &

ingredients

• Cosmeceutical– The FDA does not recognize this term which is

analogous to Japan’s “quasi-drug” category.29

GMP for Cosmetics

“Although there are no good manufacturing practice (GMP) regulations for cosmetics, we do have Good Manufacturing Practice Guidelines (Inspection Checklist). Failure to adhere to GMP may result in an adulterated or misbranded product.”

http://www.fda.gov/Cosmetics/GuidanceComplianceRegulatoryInformation/ComplianceEnforcement/ucm136455.htm

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We are a “self-regulated” industry . . .

REMEMBERWhile we may be “self-regulated”

the FDA has ultimate authority over cosmetics too!

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Consumer Commitment Code (2007)•Cosmetic Ingredient Review Expert Panel•Voluntary Cosmetic Reporting Program •Report Adverse Experience to the FDA•Maintain Safety Information Summary