VALIDATION STRATEGIES FOR MULTI-PRODUCT FACILITIES

Transcription

1 VALIDATION STRATEGIES FOR MULTI-PRODUCT FACILITIES By: Justin Roose Head Validation Engineer Product Quality Assurance (Global Compliance) 1

2 Session Agenda 1. Instruction 2. Questions 3. Do it! Open-forum training session Two-way dialog Your experiences 2

3 Group Activities Determine multi-product validation strategies (scenarios) Break into teams Scribe Presenter 3

4 Multiple products or Mixed-use? Session discusses both Concepts are the same Solved by understanding the product and other business lines 4

5 Multiple products or Mixed-use? Very similar product formulae Variety of sunscreen products Same type/business line Variety of oral OTC drugs Mixed-use (cross business-line) Drug/Cosmetic/Supplement/Foods/ Biologics/Device 5

6 Considerations for various business lines Considerations based on regulations inherent to necessary controls Drug Actives, Micro (sanitizing), CPPs, Critical Characteristics Vaccine/Biologics Assay/Actives, Potency, Sterility, Micro (sterilization), CPPs, Critical Characteristics, Environmental conditions 6

7 Considerations for various business lines (con t) Device Verification & Validation, Controls, Consumer Feedback, Safety, Micro (sterilization), Bio Burden, Black/White Box Testing Foods HACCP, Raw Material Controls & Variation, Process Controls, Micro (sanitizing) Supplements Allergens, Therapeutic Ingredients Micro (Sanitation) 7

8 Business Line & Regulations Drive validation approach Regulations what do you think? (list) Many markets accept certifications from comparable or more strict audits Example 8

9 How exactly do we approach validating a mixed-use, or multipleproduct facility? 9

10 First how do we validate a single product What do you think? 10

11 Types of Validation Equipment Cleaning Facilities & Utilities Sanitizing Validation Process & Packaging Laboratory Equipment Test Methods Control & Information Systems Software

12 Validating a mixed-use, or multipleproduct facility Understand your business line requirements (ie. Pharma) Understand the product characteristics and production needs and consider them against other products. Sometimes design for most critical product need or regulation. Simple, but not easy? 12

13 Types of Validation Equipment Cleaning Facilities & Utilities Sanitizing Validation Process & Packaging Laboratory Equipment Test Methods Control & Information Systems Software

14 Questions? Multi-Product Mixed-Use Regulations Product needs Regulatory requirements 14

15 Facility What does the product require? Facility GMP/Sanitary Design Washable surfaces Drainable floors, air gaps to drains Sloped piping Sealing doors Process / Material / People / Waste Flow 15

16 Utilities Clear utility specifications per product requirements (product specifications?) business line requirements Drives the level of validation All critical utilities should be validated 16

17 Utilities Water Quality: RO, DI, WFI, other? Product requirements Validate to specification Tips for Success Design Capacity Consider manufacturing, cleaning and sanitizing needs 17

18 Group Exercise Water System Drugs & cosmetics facility. Water used for cleaning, as a raw material, sanitize rinse. What are the validation requirements for this water system (IOPQ)? Break into teams 3 minutes Scribe (laptop) Presenter 18

19 Group Exercise Water System Share - 1 minutes Team 1 Results? Do you agree? Were your results similar? 19

20 Utilities HVAC Supports product quality Prevents cross-contamination Processing & Storage Air Quality Directional: room to room (ΔP), laminar Temp & Humidity Alarms Dedicated AHUs? 20

21 Class Exercise HVAC Drug facility: Rx, OTCs. Mixing, kinetics, aseptic processing, sterile fill, general filling What are the IOPQ requirements? (list) 21

22 Utilities Steam Capacity & Quality Intended use: Sterilize, Process Heating, Facility? Cleaning & sanitizing Compressed Air (Product requirements) Capacity Quality required for the product Processing, drying 22

23 Other utilities Product Contact Utilities Capacity & Quality (specification) Nitrogen/Hydrogen/Gases Other Support Utilities Dust Collection (Cross contamination) Vacuum Potable water (sanitation, cleaning?) Glycol/Refrigerant/Mineral Oil Cleanser/Sanitizer/Disinfectant 23

24 Warehousing / Storage Raw, Bulk formula, In-process/ Intermediates, Components, Finished Goods, Rejected Material Control Storage limitations - What do you think? Reject, Spatial Separation, Labeling, Controls, Authorizations, Temperature, Humidity, Routine Monitoring Software Systems 24

25 Questions? Product Utilities Support Utilities Warehousing & Storage 25

26 Equipment Design Design & Qualify equipment for a broad range of operations Contact surface Correct materials & finishes Understand equipment capabilities and limitations Types of products it cannot support? 26

27 Equipment Qualification Define your overall IQ / OQ / PQ requirements within the protocol Document intended products within the equipment description section Challenge broad range of capability Provide justification for planned tests Consider equipment train PQs 27

28 Group Exercise Packaging Line Topical Pharma Facility Packaging Line 25 SKUs, different: Bottles & Cap Sizes Emulsions, Oral Suspensions What IQ/OQ tests to perform? Break into teams 3 minutes Scribe (laptop) Presenter 28

29 Group Exercise Water System Share - 1 minutes Team 2 Results? Do you agree? Were your results similar? 29

30 Questions? Production Equipment Qualification 30

31 Process & Packaging Validation Understand each product s needs/cpps Leverage product understanding Access your developmental work Specify process flow & major unit ops Specifications (Acceptance Criteria) Actives, Physiochemical, Micro Batch Size, Order of Additions, Process Steps & CPPs Temps, Speeds, Time, etc 31

32 Product Families What do you think? Product grouping based on similarities: Processing Steps or Addition Order Ingredients Product knowledge is key, leverage your subject matter experts. Small differences can have a big impact be honest about your processes. 32

33 Considerations What similarities allow grouping? Document in protocol Grouping justification Similarities Development / Plant Trial supporting data Demonstrate your product understanding. 33

34 Class Exercise PV Facility: Children's Acetaminophen 1 Strength: 160mg / 5 ml Flavors: Grape, Bubblegum, Cherry Batch Sizes: 500L, 1500L, 3000L What are the PV requirements? # Batches, # of Products? What to test? 34

35 Class Exercise Packaging Facility: Sunscreen Bottle Filling Bottle Sizes: 150mL, 400mL Name Viscosity Active #1 Active #2 Standard 20,000 28,000 cp 15% Avobenzone -- Kids 24,000 30,000 cp 30% Avobenzone 5% TiO 2 Max 30,000 35,000 cp 30% Avovenzone 10% TiO 2 Shimmer 22,000 30,000 cp 8% Avobenzone -- What are the test requirements? # of protocols, # of Products? # of runs? What to test? 35

36 Questions? Process Validation Packaging Validation 36

37 Cleaning Validation Definition: Documented evidence that cleaning process removes product and cleanser to acceptable limits. Cleaning Marker: Analyte(s) used to represent surface cleanliness from the target product. Typically Active Ingredient(s) Could be other ingredients (justification) Allergen 37

38 Cleaning Validation Cleanliness Standards Markers for cleanliness Carryover Limits (this, and other products) Visual Cleanliness (Qualify staff) Dirty Hold Time (DHT Clean Hold Time Value of Process Development, results support selection of cleaning families TACT 38

39 Cleaning Families What do you think? Based on similarities: Actives / Markers Similar ingredients Solubility Difficult to clean compounds Physical properties (drying, viscosity) Coupon studies and development work to classify cleaning families 39

40 Change From Campaigning & Cleaning Matrix Reduce cleaning/sanitizing and changeover (example) Full Clean: Different family Short Clean: Similar product Product flush: Similar product, higher concentration Change To: BP-1 BP-2 BP-3 BP-4 BP-5 BP-1 X WC WC WC WC BP-2 WC X DC DC DC BP-3 WC DC X DC DC BP-4 WC PF DC X DC BP-5 WC DC DC DC X Legend: Wet Clean - WC Product Flush - PF Dry Clean - DC No Clean - X 40

41 Group Exercise Facility: Sunscreen Filling Bottle Sizes: 150mL, 400mL Name Actives Other ingredients Cleanser Family Women s Lotion Octocrylene 15% Fragrance, Color Base (ph 12) E1 Men s Sun Octocrylene 14% Base (ph 12) E1 Moisturizing Ocrocrylene 5% Silicone Base (ph 12) E2 Germ-gone Ethyl Alcohol 70% Gel Water G1 Premium Gel Ethyl Alcohol 70% Gel, Fragrance Water G1 AB Moisturizing Ethyl Alcohol 70% Gel, Vitamin E Water G1 Validation requirements 4 min # of validation protocols? Testing requirements? 41

42 Group Exercise Water System Share - 1 minutes Team 3 Results? Do you agree? Were your results similar? 42

43 Sanitizing/Sterilizing Validation Definition: Documented evidence that sanitizing process reduces microbes to acceptable limits. Standards Sanitizers Microbial Limits Bioburden / Log-reduction Sanitized Hold Time (storage conditions) Single (1) method possible 43

44 Class Exercise Sanitizing Facility: Mixed-Use Bulk Mixing. Medicated Ointment 1000 cfu/100cm 2 Topical Pharmaceutical 1000 cfu/100cm 2 Fish Oil Products (3) 300 cfu/100cm 2 Sanitizing Validation? How many Sanitizing Validations? How many Sanit Processes? 44

45 Questions? Cleaning Validation Sanitizing Validation 45

46 Multi-Product and Mixed-Use Scenarios Classroom Exercises & Tips for Success 46

47 Same Product Family Scenario: Multiple products with the same active ingredient. Hydrocortisone 0.5% 150mL tubes Hydrocortisone 1.5% 150mL tubes Hydrocortisone 0.5% 30mL tubes Hydrocortisone 1.5% 30mL tubes Process Validation Requirements? Packaging Validation Requirements? # of Sanitizing Validations? 47

48 Considerations Same Product Families How similar is the manufacturing process? CPPs / Product specifications Fewer Process & Packaging Validations Likely same equipment utilized (IOPQs) Possibility for bracketing approach 1 worst case cleaning 48

49 Mixed Families Scenario: Multiple families, same business line. Different oral analgesic suspensions Acetaminophen 160mg/5mL Acetaminophen 350mg/5mL Ibuprofen 100mg/5mL Ibuprofen 250mg/5mL PV, Cleaning? Equipment Qualification? 49

50 Considerations Potentially similar equipment Different cleaning requirements, but potentially similar cleaning methods. May be possible to establish one cleaning family Worst case product Likely similar or representative sanitizing 50

51 True mixed-use Scenario: Drugs, Cosmetics & Supplements Different raw material purity requirements Varying cleaning/micro requirements Documentation requirements (such as 2nd person verification, in-process release requirement) What different storage, handling & control requirements? 51

52 Considerations Food/Supplement HACCP requirements needed for food Raw material control and storage is more critical for Supplements Allergen storage limitations Cross contamination Robust sanitizing & environmental monitoring programs 52

53 Ingestible Drug / Nondrug products Many policy & procedures default to drug production for mixed-use. Qualification and Validation only required for drug products. But, consider cleaning for non-drug, carryover risk! Enforce GMPs for all production, or only drug? Pros & Cons? 53

54 Dedicated equipment? Risks: Cleaning / micro, cross-contamination Complicated, time consuming to manage Extreme controls needed Examples: Heart medication (low dosage) Controlled substances Penicillin Kosher / Halal certification 54

55 Questions? Multi-product scenarios Mixed-use scenarios 55

56 Policy & Procedures to support Multi-Product and Mixed-Use Facilities 56

57 Validation Policy Specify the scope of which business lines / products require validation Outline requirements by validation type Facility & Utilities Equipment Qualification Process & Packaging Validation Cleaning & Sanitizing Validation Lab Equipment & Methods Software Validation 57

58 Procedures for Supporting Quality Systems Validation Procedures Quality Manual Master Validation Plan Change Control GMPs & GDPs, Gowning & Access Cleaning, Sanitizing/Sterilization Training 58

59 Session Summary Demonstrate Product / Process knowledge Understand regulation requirements Provide Justification Summarize your validation program for audit compliance and alignment Consider product interactions 59

60 Questions? 60

61 Thank you! Justin B. Roose, Head Validation Engineer Global Compliance, Amway Corp Fulton St. East, Ada MI, Bldg 52-2J Biography Justin Roose Justin is a Lead (Head) Validation Engineer at Nutrilite / Amway Corp in Ada, MI. He is currently leading validation activities in a new 4-phase production facility. His team is responsible for: process, packaging, cleaning, sanitizing and software validation, as well as equipment and utility qualification. His software validation team is also responsible over 25 corporate software systems used to govern GMP functions in North American Operations. Justin received his BS in Chemical Engineering from Calvin College. He has obtained over 15 years of experience, across the pharmaceutical, vaccine, biologics, foods and nutritional supplements fields. Since joining Amway Corp in 2006 Justin has created and implemented an effective change control program, led the Validation Department, and created software & process/packaging validation programs. 61