Industries: Pharma / Biotech

Best Practices for an Effective Cleaning Validation Program

Course Director: Steven Weitzel

Course Description - Course runs 9:00 to 5:00 both days

This course provides practical guidance on cleaning validation regulatory compliance, in conjunction with process validation principles to facilitate reasonable and informed decision making and activity planning.  Regulatory requirements and the latest industry practices will be included in the discussion to identify questionable practices that may be misdirected as well as the better practices that support and align with current process validation principles. The program will describe a risk-based approach for establishing an effective cleaning validation program, including the development of policies, master plans and the appropriate content for each study to be performed incorporating critical quality attributes and critical process parameters and process control. In addition, validation maintenance and life cycle aspects will be reviewed. Cleaning validation examples will be included from different sterile and non-sterile product types, and different types of dosage forms including oral, topical, and injections. Concepts will apply to any FDA regulated manufacturing including drugs, supplements, personal care, medical devices. Additional benefits of this class include interacting and learning from peers. Participants will have the opportunity to discuss their challenges and problems.

Additional benefits of this class include interacting and learning from peers. Participants will have the opportunity to discuss their challenges and problems.

This course has been pre-approved by the Regulatory Affairs Professionals Society (RAPS) as eligible for 12 credits towards a participant's RAC recertification upon full completion.

Who Should Attend

Attendance at this two-day course will be beneficial to personnel directly involved or supporting the development of cleaning validation programs and plans, also those responsible for cleaning validation protocols and execution activities, as well as beginning or experienced personnel who may eventually participate in such efforts. This includes validation, engineering, operations, and laboratory personnel, also Analytical Method Development, Quality Control and Quality Assurance personnel.

Individuals in management who interact internally with these teams or externally with regulatory agencies will also benefit from attending this course.  There are no prerequisites for attending, but a basic knowledge of general science and process validation is helpful.

First Day

Compliance Overview

Why Clean? Manage Risk of Batch to Batch Contamination

  • Contamination Types and sources
  • Contamination Control and Process Strategies
    • Single-use, dedicated, campaigns
  • Cleaning Validation Compliance Scope

Regulatory Aspects

  • Cleaning validation Guidelines, & Expectations
    • US FDA
    • EMEA
    • PICs, organizations
  • Regulatory trends -Process Validation
  • Regulator concerns about cleaning validation
    • Cleaning validation Establishment Inspection Reports (EIRs), FDA 483 observations and Warning Letters.

Review of Industry Practice

  • Approach to Process understanding and control
  • Approach to Residue Risk and Limits
  • Approach to Inspection and Sampling
  • Cleaning Validation Management-Typical elements of a policy/program

Better Practices to Implement a Robust Cleaning Validation Program

Evaluate Equipment and Residues- Risk Assessment

  • The information gathering process
  • Equipment/product matrix>Substrate/residue matrix
  • Equipment use type and use patterns
  • Qualitative residue risk assessment

Cleaning Process Fundamentals

Define and Control Critical Process Parameters (CPPs)

  • Review of current cleaning processes/procedures
  • Agents-Select and Justify the right Cleaning Agents for your Substrate/residue
  • Methods- Immersion, film flow, impingement, pipe flow, defining adequate parameters to provide consistent results
  • Procedural Aspects
    • CIP vs. COP; Manual vs. Automatic- advantages and disadvantages
    • Sequence, Duration, Interval, pattern, direction
    • Other Time Concepts- dirty hold time (DHT) and clean hold time (CHT)

Establish Scientifically Sound Contamination Limits

  • Convert Qualitative risk to Quantitative risk: Health based contamination levels
    • Maximum Allowable Carryover (MAC) vs. Acceptable Daily Exposure (ADE)
    • Drug Activity-Minimum Therapeutic Dose, Largest Daily Dose
    • Toxic, Allergenic and other bioactive materials
  • Purity(adulteration) based limits approach and calculations
  • Residue Contamination Risk Matrix
  • Critical Quality Attributes-Surface Acceptance Limit (SAL)
  • Use of visual criteria for determining if equipment is clean

Second Day

Better Practices to Implement a Robust Cleaning Validation Program (cont.)

Develop and Qualify Inspection and Control Methods

  • Inspection, Sampling , Monitoring Methods
    • Sampling rationale and impact
    • Choice of sampling type (visual, swab, rinse) Special topic -Visual analysis
    • Process Indicators and control scheme- type, frequency, timing
  • Analytical, Laboratory, Validation Issues
    • Specific vs. Non-specific Methods
    • Suitability, sensitivity and specificity issues (LOD/LOQ)
    • Analytical Method development, validation
    • Recovery studies, qualification sample method; special topic- rinse qualification
    • Special topic -Visual analysis and inspection

Select and Justify Acceptance Criteria and Qualification Test Plans

  • How to convert batch limits and surface limits to sample acceptance criteria
  • Special Topic- How to avoid unrealistic “worst case” traps
  • Calculated criteria vs. documented process capability
  • The correct way to implement a Grouping/matrix concept: How to use product/equipment matrix and risk matrix to select protocol challenge conditions, worst case products & equipment and determine acceptance criteria
  • Process Performance Qualification-Understanding the validation space

Install a Life Cycle Management Program for Cleaning Validation Maintenance

  • Process Life Cycle Overview
  • Flexible Management, Organization and Documentation practices
    • Master plans, area plans, protocols, reports
  • Organizing for Ongoing, Incremental Process control and Improvement
    • Process Development Guidelines
    • Continuous Process Verification; Post Validation Monitoring after equipment cleaning (Visual Inspection and Type and Frequency of Sampling/Testing)
    • Planned reviews and assessment
    • Revalidation and Change Control (Known vs, Hidden Change)

Discussion Topics and Forum

  • Microbiological aspects of a cleaning validation program for manufacturing equipment
    • Cleaning impact on viable contamination (Clean Hold Issues)
    • Cleaning, Sanitization and sterilization after use versus before use
  • Issues for Specific Sub-Industries and Related Manufacturing Facilities
    • Active Pharmaceutical Ingredient (API) Manufacturers
    • Biotechnology Facilities
    • Dietary Supplement Manufacturers
    • Cosmetic Manufacturers
  • Best Practices Going Forward-The future of cleaning processes and cleaning validation
    • Containment Concept, EMEA, and ISPE
    • Use of Disposable Equipment
    • New innovative equipment design facilitating easier cleaning
    • New cleaning technology (e.g. sprayball design)
    • New surface analyzers

Learning Objectives

By the end of this course attendees will:

  • Understand the importance and underlying principles of validation of cleaning procedures for manufacturing equipment
  • Understand the FDA requirements and perspectives on cleaning validation and areas of regulatory concern during inspections and identify gaps in their own programs
  • Be able to set up cleaning validation practices, procedures, protocols and reports that meet current FDA, WHO, PIC/S and EU regulations and align with current process validation principles including understanding of critical process parameters, sources and control of variability, process monitoring and control scheme
  • Be able to develop and defend your own rigorous but pragmatic cleaning validation approach to avoid costly rejections by regulatory agencies, but also avoid unnecessary activities and overkill

Testimonials

"I found the course to be useful in establishing a general outline of what will be required when moving to a matrix approach to our cleaning validation program. I found course materials and the instructor to be very knowledgeable and helpful." Dean R., Senior Technician, Teva Pharmaceuticals
"Good amount of material and well presented. Excellent job engaging attendees and tailoring discussion." TJ W., Lead Investigator, Adhesives Research
"Good presentation. I now have a better understanding of Cleaning Validation and I can start applying what I learned immediately to ensure that my firm is in full compliance." Jaime S., Director - Regulatory Compliance, MeriCal, Inc.
"The Course Director was very good at encompassing all I wanted. There were good examples and sample problems. I enjoyed the small group setting that allowed easy interaction with the instructor. We had good group discussions/debates and worked out problems well together. An excellent course for beginner CV personnel." Kristen H., Process Validation Engineer, Shire HGT
"This was an excellent seminar - the best Cleaning Validation training I have ever attended! The Course Director was an engaging presenter. This seminar is applicable to both new and seasoned professionals that are interested in learning about cleaning validation." Samuel L., Site General Manager, ISP