Advanced therapies such as cell therapies, gene therapies, and tissue-engineered products need strict release testing before they can be used. These products are different from traditional medicines because they often contain living cells or genetic material. Small changes during manufacturing can affect their quality, and performance.

Release evaluation checks that every batch meets approved quality standards before it reaches patients. It helps manufacturers confirm that the product is safe, and suitable for clinical or commercial use. In this article, you will learn about the most important release evaluation requirements for advanced therapies and why each one matters.

Top 10 Release Testing Requirements for Advanced Therapies

Release evaluation is the final quality review before an advanced therapy is released. Every test measures a different quality attribute, and together they show whether the product is ready for patient use. The following requirements form the foundation of a strong release testing program.

1. Identity Testing Confirms the Product Is Correct

Identity testing verifies that the final product matches the approved product profile. It also confirms that no sample mix-up happened during manufacturing or packaging. This step is especially important for autologous therapies because each product is made for a specific patient.

Before the final release decision is made, laboratories perform several tests to confirm product identity.

Identity testing may include:

• Cell surface marker analysis using flow cytometry

• DNA or RNA fingerprinting

• Genetic sequencing for engineered products

• Biomarker confirmation

• Patient sample matching for autologous therapies

• Product-specific molecular assays

Identity testing also supports chain of identity throughout manufacturing. Every verified result creates a documented link between the starting material and the finished product. This reduces the risk of product mix-ups and supports regulatory inspections.

2. Sterility Testing Checks for Bacteria and Fungi

Sterility testing confirms that harmful microorganisms are not present in the final product. Since advanced therapies are often given by injection or infusion, even a small amount of contamination can create serious health risks. A failed sterility test usually prevents product release.

Several laboratory methods are available to verify sterility before a batch is approved.

Sterility testing may involve:

• Traditional culture methods

• Automated microbial detection systems

• Rapid sterility testing platforms

• Environmental monitoring review

• Media fill validation records

• Manufacturing process verification

Many advanced therapies have very short shelf lives. Waiting weeks for traditional culture results is not always practical. Rapid sterility testing helps shorten release timelines while maintaining reliable quality control.

3. Mycoplasma Detection Finds Contamination That Is Easy to Miss

Mycoplasma are very small microorganisms that can contaminate cell cultures without obvious signs. Unlike common bacteria, they do not always make culture media cloudy or change the appearance of the product. They can still damage cells and affect product performance.

Laboratories use dedicated methods because standard sterility tests may not detect mycoplasma.

Common mycoplasma detection methods include:

• PCR-based testing

• Culture methods

• DNA staining techniques

• Rapid nucleic acid amplification tests

• Validated commercial detection kits

• Laboratory contamination controls

Fast PCR testing allows manufacturers to detect contamination much earlier than traditional culture methods. Production facilities also monitor raw materials, and cleanrooms to reduce contamination risks before manufacturing begins. Good contamination control protects product quality and reduces batch failures.

4. Potency Testing Confirms the Therapy Can Do Its Job

An advanced therapy must show that it performs its intended biological function before release. Potency testing measures this activity using validated laboratory assays. The selected test depends on how the therapy is designed to work inside the body.

Different products require different potency assays to measure biological activity accurately.

Potency testing may include:

• Cell killing assays

• Cytokine release measurements

• Gene expression analysis

• Functional receptor activation tests

• Enzyme activity assays

• Cell proliferation studies

Developing a reliable potency assay often takes significant scientific work because biological systems naturally vary. Manufacturers validate these methods to improve repeatability and accuracy. Consistent potency results help confirm that every released batch performs within approved limits.

5. Viability Testing Measures the Health of Living Cells

Many advanced therapies rely on living cells to provide the intended treatment effect. Those cells must stay healthy during manufacturing, and handling. Viability testing measures the percentage of living cells before product release.

Several laboratory techniques are available to evaluate cell health and survival.

Viability testing commonly uses:

• Trypan blue exclusion

• Flow cytometry viability dyes

• Fluorescent cell staining

• Automated cell counters

• Metabolic activity assays

• Live and dead cell imaging

Low viability may reduce treatment effectiveness even when other release tests meet specifications. Manufacturers define minimum viability acceptance criteria during product development and validation. Routine viability testing helps ensure every released product contains enough healthy cells for its intended use.

6. In-Process Testing Monitors Quality During Manufacturing

Release evaluation does not begin after manufacturing is complete. It starts while the product is still being made. In-process testing helps you identify changes early so they can be corrected before they affect the final batch.

Throughout production, laboratories collect samples and monitor important quality attributes.

Common in-process testing includes:

• Cell count monitoring

• Cell viability measurements

• pH monitoring

• Nutrient and metabolite analysis

• Process parameter verification

• Intermediate sample testing

These results help manufacturers keep the process within approved limits from start to finish. Early monitoring also reduces the chance of batch failures and unnecessary material loss. A strong in-process testing program supports consistent release evaluation results for every production batch.

7. Endotoxin Testing Confirms the Product Is Safe for Administration

A product can pass sterility testing and still contain bacterial endotoxins. These toxins remain after certain bacteria break down and can trigger fever, or severe immune reactions. Endotoxin testing helps confirm that the product meets safe limits before release.

Laboratories use validated methods to measure endotoxin levels with high accuracy.

Endotoxin testing may include:

• Limulus Amebocyte Lysate (LAL) assay

• Chromogenic endotoxin testing

• Turbidimetric methods

• Gel clot testing

• Endotoxin standard curve verification

• Quality control sample analysis

Acceptance limits depend on the product type and how it will be administered. Every testing method must be validated to produce reliable and repeatable results. Accurate endotoxin testing adds another layer of protection before the therapy reaches patients.

8. Purity Testing Measures Unwanted Materials

The finished product should contain the intended therapeutic material with as few impurities as possible. Purity testing identifies unwanted substances that may remain after manufacturing or purification. These results show whether the manufacturing process has removed contaminants effectively.

The exact tests depend on the product design and the manufacturing process.

Purity testing may evaluate:

• Residual host cell proteins

• Residual DNA

• Process-related impurities

• Unwanted cell populations

• Protein aggregates

• Manufacturing reagent residues

Manufacturers build purification steps into production to reduce impurities before release evaluation begins. Final purity testing confirms that impurity levels remain within approved specifications. These results support product consistency, and regulatory compliance.

9. Stability Testing Determines Shelf Life

Advanced therapies often remain stable for much shorter periods than conventional medicines. Stability testing shows how long the product maintains its approved quality under defined storage conditions. The results support expiration dates, and transportation requirements.

Several studies are performed to evaluate product stability over time.

Stability programs may include:

• Real-time stability studies

• Accelerated stability testing

• Temperature excursion studies

• Cryopreservation evaluation

• Shipping validation

• Storage condition monitoring

The collected data help manufacturers understand how temperature, and transportation affect product quality. Healthcare providers also use this information when handling therapies after delivery. Accurate stability data help ensure patients receive products that still meet release specifications.

10. Documentation Review Supports the Final Release Decision

Laboratory test results alone cannot approve an advanced therapy for release. Manufacturers must also review production records, quality documents, and investigation reports before making the final decision. This review confirms that every manufacturing step followed approved procedures.

Before a qualified person authorizes product release, several records are examined.

Documentation review typically includes:

• Batch manufacturing records

• Laboratory testing reports

• Equipment calibration records

• Environmental monitoring data

• Deviation and investigation reports

• Certificate of analysis preparation

Documentation review brings all quality information together in one place before release. Complete records also support product traceability and regulatory inspections. Careful documentation helps confirm that every released batch meets established quality requirements.

Conclusion

Release testing helps confirm that advanced therapies are safe, and ready for patient use. Identity testing, sterility testing, mycoplasma detection, potency testing, viability testing, in-process assessment, endotoxin testing, purity testing, and documentation review each verify a different part of product quality. Together, these requirements reduce manufacturing risks and support reliable product release.

Because advanced therapies often contain living cells or genetic material, every release decision depends on accurate testing and strong quality control. Validated methods, and complete documentation all support consistent product quality. Xellera Therapeutics understands the importance of comprehensive  release evaluation and quality systems that help advanced therapies meet regulatory expectations while supporting patient safety.