Pharmaceutical packaging directly influences the safety, stability, and overall performance of drug products. The USP <661> series defines how plastic materials and packaging systems must be evaluated to confirm that they are appropriate for pharmaceutical use. For quality, regulatory, and product development teams, the standard is a key reference for:
- identifying packaging-related chemical migrants,
- assessing how materials interact with formulations, and
- demonstrating compliance during development and commercial manufacturing.
BA Sciences, an FDA-registered and ISO/IEC 17025-accredited laboratory, supports these requirements with extractables and leachables testing services aligned with the USP <661> framework.
Understanding Extractables and Leachables
Extractables are chemical compounds that can be drawn out of packaging materials under exaggerated laboratory conditions. Leachables are substances that migrate into a drug product under normal storage or use. Both categories are central to evaluating whether packaging materials meet the expectations outlined in USP <661.1> Plastic Materials Of Construction and USP <661.2> Plastic Packaging Systems For Pharmaceutical Use.
Testing for extractables and leachables helps manufacturers understand:
- how polymeric materials behave when exposed to solvents, heat, or stress,
- which compounds could migrate into a formulation over time, and
- whether any of those compounds pose quality, stability, or toxicological risks.
Common analytical tools include gas chromatography (GC), mass spectrometry (MS), and inductively coupled plasma spectroscopy (ICP), which detect chemical species at trace levels. FDA, USP, and PQRI guidance all reinforce that extractables and leachables studies are essential for demonstrating packaging suitability.
BA Sciences conducts extractables and leachables evaluations aligned with the USP <661> series, applying validated methods to vials, bottles, closures, and complete packaging systems. By combining chemical characterization with toxicological assessment, laboratories help ensure that potential leachables remain within acceptable limits and do not compromise drug quality or patient safety.
The Impact of USP <661> on Pharmaceutical Packaging
The USP <661> series outlines how plastic materials and packaging systems must be evaluated to ensure they are appropriate for pharmaceutical use. It is divided into two core chapters:
- USP <661.1> Plastic Materials Of Construction — focused on testing raw polymers used to manufacture packaging.
- USP <661.2> Plastic Packaging Systems For Pharmaceutical Use — focused on finished containers, components, and systems intended to hold drug products.
Together, these chapters establish expectations around physical, chemical, and biocompatibility performance to safeguard product quality throughout the drug lifecycle.
Key Compliance Considerations
Manufacturers must demonstrate that packaging materials:
- do not interact with formulations in ways that affect stability or safety,
- meet identity and purity requirements,
- limit extractables and leachables to safe levels, and
- remain suitable for use across storage and distribution conditions.
Challenges often arise from polymer variability—such as additives, processing aids, or residual monomers—which can migrate into formulations. To address these risks, companies use material characterization studies, toxicological risk assessments, and analytical testing aligned to the USP <661> framework.
Challenges and Solutions in Implementing USP <661> Guidelines
Implementing the USP <661> series can introduce both technical and operational challenges for pharmaceutical manufacturers. Many organizations are transitioning from legacy packaging materials or adopting newer testing protocols, and gaps in historical data often complicate compliance efforts.
Common Challenges
- Legacy materials requiring requalification: Older polymers or packaging components may not meet current expectations under USP <661.1 or USP <661.2.
- Incomplete documentation: Missing data packages or historical test information can delay material assessments.
- Evolving analytical sensitivity: Modern extractables and leachables testing often requires more sensitive instrumentation than past methods.
- Complex supply chains: Multiple material suppliers or changes in processing conditions may impact consistency and require additional evaluation.
Practical Solutions
A structured, proactive approach supports smoother compliance:
- Start with a risk assessment: Identify high-risk materials, components, or drug–packaging interactions early in development.
- Use predictive modeling: Polymer chemistry and additive profiling can help anticipate potential extractables before formal studies begin.
- Strengthen quality control practices: Applying consistent procedures—from material selection to lot release testing—helps maintain control over chemical migrants.
- Collaborate with qualified laboratories: Partnering with accredited labs ensures testing remains aligned with current USP <661> expectations and analytical best practices.
By combining material science knowledge with modern analytical strategies, manufacturers can meet the intent of USP <661> while reducing delays, rework, or packaging-related quality risks.
Regulatory Compliance and Quality Control in Pharmaceutical Packaging
Within the USP <661> framework, regulatory compliance and quality control work hand in hand to ensure that packaging is suitable for its intended pharmaceutical use. Agencies including the FDA, EMA, and other global authorities expect manufacturers to implement validated processes that verify material identity, safety, and consistent performance across the product lifecycle.
Core Compliance Expectations
To maintain alignment with USP <661> and broader regulatory requirements, manufacturers typically rely on:
- Material verification — confirming that polymers and additives match approved specifications.
- Biocompatibility assessments — evaluating whether materials meet safety expectations for patient exposure.
- Periodic requalification — reassessing packaging systems over time to ensure nothing in the material supply chain, formulation, or manufacturing environment has changed.
- Robust documentation — maintaining clear data packages that support regulatory submissions and inspections.
Evolving Guidance
Regulatory bodies and industry groups—such as the Pharmaceutical Quality Research Institute (PQRI) and the U.S. Pharmacopeia—continue to refine expectations around analytical sensitivity, toxicological evaluation, and risk-based decision-making. These updates guide laboratories and manufacturers toward more predictive and thorough extractables and leachables assessments.
By consistently following USP <661> guidance and integrating strong quality control practices, organizations can demonstrate full control over their packaging systems, reduce the likelihood of recalls or quality failures, and support global market access. Ongoing collaboration with accredited laboratories keeps testing aligned with current regulatory trends and industry standards.
The Path to Safer Pharmaceuticals
The USP <661> series remains a core standard for ensuring pharmaceutical packaging is safe, stable, and suitable for its intended use. By prioritizing extractables and leachables evaluation, manufacturers gain confidence that packaging materials consistently meet regulatory, toxicological, and performance expectations.
For teams in quality assurance, regulatory affairs, and product development, understanding USP <661> extractables and leachables requirements helps safeguard patient health and maintain lifecycle control over packaging systems. As testing technologies evolve and global standards continue to shift, partnering with experienced laboratories ensures compliance remains strong and up to date.
Partner With BA Sciences
BA Sciences provides extractables and leachables testing services aligned with USP <661>, supported by FDA registration and ISO/IEC 17025 accreditation. Our team helps pharmaceutical manufacturers evaluate materials, address regulatory expectations, and maintain packaging quality across development and commercial production.
Contact BA Sciences to discuss extractables and leachables testing or support with USP <661> compliance.