PEIpro^®-GMP

Description

PEIpro^®-GMP manufacturing process

PEIpro^®-GMP is manufactured according to a validated manufacturing process in compliance with GMP guidelines to ensure traceability from starting material to the final product. GMP guidelines for manufacturing of ATMPs requires that the quality of raw materials be of pharmaceutical grade when available to avoid contamination and to minimize the variability of raw material (ICH Q7 and EudraLex Vol 4, Part IV, 7.13). Using GMP grade transfection reagent as raw material will address these guidelines, whilst mitigating risk across the supply chain.
To address this requirement, both steps of PEIpro^®-GMP manufacturing (chemical product and fill & finish) are uniquely managed in compliance with GMP guidelines (Fig. 1).

Fig 1. Manufacturing process of PEIpro^®-GMP reagent.

Continuous control testing of PEIpro^®-GMP are performed on starting material, bulk chemical product and formulated sterile product to ensure consistency in identity, potency, purity and safety at each step of the manufacturing process.

We perform an extensive list of Quality Controls (QCs) in addition to those required by current GMP guidelines according to European Pharmacopeia, making PEIpro^®-GMP transfection reagent the first and only transfection reagent that meets highest quality standards for therapeutic viral vector manufacturing. The full list of QCs is available upon request:

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Guaranteed seamless transition from clinical trials to commercialization of viral therapies

PEIpro^®-GMP is the highest quality grade PEI transfection reagent for use as raw material in the production of viral vectors (eg. AAV, lentivirus) intended for Human ATMP clinical trials and commercialization. With PEIpro^®-GMP to complete the PEIpro^® product range, the transition from process development up to commercialization is a straightforward and seamless process.

To ensure validation process for commercialization, scale-up or scale-out of therapeutic virus production with PEIpro^®-GMP are guaranteed to be comparable to production yields achieved at small scale with R&D grade PEIpro^® for process development and with PEIpro^®-HQ for preclinical and early clinical trials (Fig. 2).

Fig. 2. Reproducible virus titers are achieved with different grades of PEIpro^®. Suspension 293-T cells were seeded at 1 x 106 cells/mL in FreeStyle™ F17 medium and transfected with PEIpro^®, PEIpro^®-HQ and PEIpro^®-GMP reagents following the same protocol. AAV were produced with the Helper Free Packaging System (Cell Biolabs) and titers were measured 72h after transfection using a GFP reporter gene expression assay.

PEIpro^®-GMP conditioning for flexibility and cost-efficiency

Bags with MPC connectors and weldable tubing for “plug and transfect” systems

Closed-systems and single-use technologies are growingly used for clinical trials and commercial manufacturing of viral vectors. We provide two sizes of PEIpro^®-GMP in bags to ensure aseptic connections to successfully perform large-scale transfection in closed sterile systems.

Each PEIpro^®-GMP bag is fitted with c-flex tubing that can either be welded or used with MPC connectors, which ensures compatibility with all stirred-tank and fixed-bed bioreactors (Fig. 3). With PEIpro^®-GMP bags, preparation of large-scale complexes is simplified and guaranteed sterile with a simple “plug and transfect” closed system; thereby considerably reducing contamination risks. Should your closed system require a special configuration, please contact us here:

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Fig 3. Example of a PEIpro^®-GMP bag: PEIpro^®-GMP 1 Liter bag with MPC connectors and weldable tubing. PEIpro^®-GMP is also available in 300 mL bag.

Flexibility and ease of use

We also provide PEIpro^®-GMP in bottle conditioning of 10 ml or 100 ml to adapt to different manufacturing processes for scale-up and scale-out strategies. PP or PEGT bottles offer the flexibility that is needed, notably when choosing a scale-out strategy to define the amount of viral vector needed (eg. for autologous CAR-T cell therapy).

Mitigate your risk management process

The introduction of any starting or raw/ancillary material in the manufacturing process of ATMPs adds potential risk factors. It is therefore essential to evaluate each raw material individually through a risk-based approach. By using PEIpro^®-GMP as the transfection reagent to produce viral vectors, you can be confident that quality and safety are ensured:

• PEIpro^®-GMP is manufactured in compliance with international GMP guidelines ICH Q7 and correspondingly with EU “Guidelines for good manufacturing practices for medicinal products for human and veterinary use” (ICH Q7 and EudraLex Vol 4, Part II and Annex I: Manufacture of Sterile Medicinal Products). The manufacturing process of PEIpro^®-GMP is fully documented.
• PEIpro^®-GMP is provided in bags with MPC connectors and weldable tubing suitable for use in closed systems to decrease contamination risks.
• The aseptic manufacturing process is validated through the performance of media fill tests (MFT).
• The quality of PEIpro^®-GMP is continuously assessed during the manufacturing process in compliance with GMP control testing guideline. Extensive Quality Controls to assess Identity, Potency, Purity and Safety.
• Incoming testing protocols as well as incoming satellite sample are available upon request.

Quality

Expert Regulatory and Technical support teams

Are you concerned about future changes in regulation? Do you need more insight on current regulation for market authorization? With more than 25 years of combined experience in the development and manufacturing of GMP compliant transfection reagent for Cell and Gene Therapy, our Regulatory Support Team is there to accompany each of you by offering their regulatory expertise.

We offer regulatory support for your IND applications to the US FDA and for submission to any European Regulatory Agency with:

• the Drug Master File (DMF) on file with the US FDA that can be cross-referenced in IND applications and BLA (Biological License Application) to the US FDA.
• the documentation describing the Chemistry, Manufacturing and Control (CMC) for IMPD submission or Marketing Authorization to any European Regulatory Agency.

Dual sourcing

As a supplier of a critical component for the manufacturing of ATMPs, we critically analyzed how we could mitigate the risk associated with being the unique sourcing of transfection reagent PEIpro^®-GMP, the number #1 transfection reagent used worldwide for the development of ATMPs for gene therapy. We’ve put in place a dual sourcing approach for PEIpro^®-GMP that we entirely manage. This allows ATMP manufacturers to have all the advantages of dual sourcing (production capacity, lead time), while dealing with one single point of contact: us! With this approach we are able to guarantee product uniformity from both sourcing of PEIpro^®-GMP.

• Identical quality grade of PEIpro^®-GMP (GMP part II, Annex I)
• Identical Quality Controls performed on PEIpro^®-GMP
• Identical efficiency of PEIpro^®-GMP (assessed by product activity comparison)
• A validated manufacturing process as well as the Aseptic Process validation

Contact us

We welcome audit request from customers to qualify Polyplus-transfection^® as an approved supplier of raw materials used in the manufacturing of clinical grade therapeutic products. Please contact us here if you would like to perform an audit of our Quality Management System and facility.