Usually, it takes around four to nine months to manufacture a plasmid under GMP (Good Manufacturing Practice). The reason why it takes so long to produce a plasmid under GMP is that an entirely different level of quality control and control is required to ensure a GMP plasmid is appropriate for injecting into humans. HD plasmid manufacturing enables high supercoil and low endotoxin plasmid preparations suitable for use as a raw material in GMP manufacturing. This article sheds light on the GMP plasmid manufacturing procedure.
Phases of the GMP plasmid manufacturing project
The typical contract plasmid manufacturing project under GMP consists of three phases. These three phases are planning, process development, and production.
● Planning Phase
The planning phase of a plasmid manufacturing project involves the execution of important agreements and project discovery. It is vital to execute a two-way confidentiality agreement between the HD plasmid manufacturing company and the client. Next, a plasmid questionnaire has to be filled out by the client so that the information gathered can be used to generate a detailed manufacturing proposal.
Some plasmid manufacturing companies also sign the Manufacturing Services Agreement (MSA) to spell out the terms and conditions of the project. It is after signing the Purchase Order (PO) that clients are invited to perform the quality audit to ensure that regulatory requirements are being met.
● Process Development
Process development is essential for ensuring the success of scale-up operations and maximization of plasmid quality and yield. It usually consists of strain and clone selection, fermentation, and purification development.
● Production Phase
Finally, HD plasmid manufacturing commences under GMP. Production takes place in five steps:
1. Cell banking:
In this step, master and working seed banks are produced by using bacterial strains and these are preserved in liquid nitrogen storage. The master seed bank works as a repository for the cells, while the working seed bank is actively used for the production of the plasmid.
2. cGMP production- fermentation and purification:
Plasmid fermentation can be performed in batch or fed-batch mode. Master or working seed banks are fermented to a high density and harvested to grow bacteria containing the plasmid. The bacteria are then lysed to release their cellular contents, including the plasmid. Next, the plasmid is purified, and subsequently, the purified plasmid is concentrated and desalted.
3. Bulk drug substance release testing:
Once the drug is produced in bulk, release testing is performed using endotoxin, pH, microbial enumeration testing, and other techniques.
4. Aseptic fill/finish:
In this step, the bulk product is filtered and filled into vials as specified by the client.
5. Drug product release testing:
Finally, once the product is filled, it is delivered to the quality control center for final release testing.
When it comes to manufacturing plasmids using the GMP production method, most companies follow these three phases. It can take about four to nine months depending on the steps used by the manufacturer to produce the plasmid. The planning phase usually takes 1-2 months, the process development phase takes 1-2 months, and the production phase takes 2-5 months.