#processvalidation

Introduction

In biopharmaceutical manufacturing, cleaning validation is far more complex than in traditional pharma due to the sensitive nature of biologics, the use of living organisms, and strict regulatory expectations. Contamination risks—whether microbial, cross-product, or endotoxin-related—can compromise product safety, stability, and regulatory compliance.

This blog explores the challenges biopharma manufacturers face in cleaning validation and provides practical, digital solutions to meet evolving compliance standards.

What Makes Biopharma Cleaning Validation Different?

Unlike small molecule drugs, biologics:

Are produced in sterile or aseptic environments

Have higher microbial sensitivity

Require larger, multi-use equipment

Often involve low batch volumes and high-value products

Hence, cleaning validation in biopharma must be:

Scientifically sound

Risk-based

Data-driven

Audit-ready

Top Challenges in Cleaning Validation for Biopharma:

1. High Risk of Cross-Contamination

Biopharma facilities often manufacture multiple products using shared equipment. Inadequate cleaning may lead to:

API residue carryover

Microbial contamination

Allergen cross-contact

Solution: *  Use worst-case product selection and validated cleaning protocols specific to equipment and product matrix.

2. Microbial & Endotoxin Control

Biologic drug products are highly susceptible to:

Bioburden

Endotoxins

Spores and pyrogens

Solution: * Include microbial swab testing and endotoxin testing in your validation protocol.

3. Complex Equipment Design

Bioreactors, filtration systems, and chromatography columns are harder to clean due to:

Internal dead legs

Long piping runs

Closed systems

Solution: * Perform equipment design reviews and validate clean-in-place (CIP) and sterilize-in-place (SIP) systems.

4. Evolving Regulatory Expectations

Agencies like the FDA and EMA expect:

Health-Based Exposure Limits (HBEL)

Quality Risk Management (QRM)

Lifecycle approach to cleaning validation

Solution: * Implement a risk-based lifecycle validation strategy supported by digital systems.

5. Documentation and Traceability

Manual records are prone to errors, omissions, and compliance gaps.

Solution: *Adopt a paperless validation system like E residue Pro to ensure:

Real-time data capture

21 CFR Part 11 compliance

Traceable audit trails

E residue Pro – A Digital Solution for Biopharma Cleaning Validation

E residue Pro by PQMS is a purpose-built cleaning validation software designed for pharmaceutical and biopharmaceutical environments.

Key Features:

Automated protocol generation for swab/rinse sampling and HBEL calculations

Real-time dashboards to track cleaning runs and approval workflows

Integrated microbial and endotoxin result tracking

Audit-ready documentation and electronic signatures

Seamless compliance with FDA, EU GMP, and GAMP 5 standards

Conclusion

Cleaning validation in biopharma is both mission-critical and highly challenging. From cross-contamination control to microbial risk mitigation, success depends on applying science-based methods and adopting digital tools for consistent compliance.

All products meeting the definition of medical devices as defined by the EU regulations require CE marking before they can be sold in the EU. CE marking indicates that a product has been assessed by the manufacturer and meets EU safety, health, and environmental protection requirements. It is required for products manufactured anywhere in the world that are then marketed in the EU.  

The product must comply with all the relevant MDD to MDR requirements of before affixing the CE marking to it.  Although the compliance requirements are similar in many ways, the European route is thought to be less governmental, resulting in shorter times to market, greater acceptance rates of new devices, and lesser costs associated with obtaining conformity certification.

While the benefits of obtaining a CE marking are significant, regulations are always subject to change. New modifications to the European medical device requirements are making the process more similar to that of the FDA when it comes to establishing conformity.

By May 2021, a new Medical Device Regulation (MDR 2017/745) will go into effect throughout the European Union. Despite the changes, there still remains a clear path to establishing conformity and obtaining a CE marking that will allow your company to access European markets.

 Steps

1.       IDENTIFY THE APPLICABLE REQUIREMENTS OF THE REGULATIONS

1.       CLASSIFY THE DEVICE AS PER THE RULES DEFINED FOR CLASSIFICATION OF MEDICAL DEVICES

2.       IDENTIFY AN APPROPRIATE ROUTE TO CONFORMITY

3.       ASSESSMENT OF THE PRODUCT’S CONFORMITY TO EU REQUIREMENTS

4.       COMPILE THE TECHNICAL DOCUMENTATION, QMS & CLINICAL EVALUATION REPORT.

5.       ASSESSMENT BY NOTIFIED BODY

6.       MAKE A DECLARATION OF CONFORMITY AND AFFIX THE CE MARK

IZiel Healthcare has collaborated with Belgium based Obelis (European Authorized Representatives) to provide a “One-Stop Solution” to fully support Class I, IIa, IIb & III medical device manufacturers across USA, Europe & Asia. Typically, all MDD-MDR transition projects initiate with Gap Assessment. Gap Assessment is a crucial activity during MDR transition.