An active pharmaceutical ingredient (API) is a specific medicine’s active component. Some drugs, such as combination treatments, contain multiple active components that treat various symptoms or operate in different ways. Inactive excipients that convey the drug to a target system, as well as the APIs themselves, are found in every pharmaceutical product.

APIs should not be confused with pure, unfiltered drugs. APIs, are key components that must be appropriately processed in order to produce safe medication for clinical use. APIs are chemicals formed by multiple chemical reactions, rather than direct raw materials.  

APIs have historically been manufactured in the home nations of pharmaceutical corporations. However, in recent years, many firms have chosen to outsource production to lower costs. This has resulted in considerable changes in the way these pharmaceuticals are controlled, with more stringent Federal Drug Administration (FDA) criteria and inspections implemented.

A checklist of important factors to optimize Project cost, timeline and smooth regulatory process in an API plant:

1. API plant manufacturing requisites:

  • Kilo lab preparation and scaling up prior to cGMP production.
  • A wide range of equipment in various sizes.
  • A regimen of preventative maintenance.
  • Records for the master batch.
  • Protocols for preventing cross-contamination
  • Organizing the warehouse and sampling raw materials
  • A dependable and experienced production staff.

2. Fastest route for API Manufacturing:

  • Because of the novelty of creating a drug substance for the first time, chemistry challenges frequently develop due to today’s more complicated APIs. At any point along the route, keeping the molecules within specifications to fulfill FDA, EMA, and ICH requirements might become a challenge.
  • The most efficient path to effective API manufacture is to start with excellent R&D that is repeatable, scalable, well-documented, and receives regulatory approval quickly.
  • It’s best to hold on to moving into the expensive GMP production suite until you’ve finished scaling up, which will reveal any chemistry difficulties in a more cost-effective setting.

 3. Best way to scale API manufacturing for commercialization:

  • The key to optimization is analytical technique development, which aids in the creation of the correct atmosphere and conditions for the creation of new molecules and the demonstration that methods achieve their intended goal.
  • Determine the method’s objective.
  • Determine the molecule’s polarity, solubility, reactivity, pH, and stability, as well as its susceptibility to air, heat, humidity, and light.
  • Check for genotoxic substances.
  • Validate the analytical procedure carefully.

4. Best way to meet the quality guidelines in API Manufacturing:

  • Follow the more than 60 ICH recommendations, which were developed to show the quality, safety, and efficacy of a newly registered product.
  • Consider the ICH rules from the beginning of a project. For a better understanding of what lies ahead, Seqens CDMO begins each project by anticipating what the FDA or EMA will demand and organizing trials and documentation appropriately.
  • From applicant to regulator, adhere to the Electronic Standards for the Transfer of Regulatory Information (ESTRI).
  • Keep up with cGMP rules released on the websites of the FDA, EMA, ICH, and other regulatory agencies.

5. Cost cutting in API Manufacturing:

  • The sponsor and CDMO teams should exchange all technical information available, including previously completed work and pertinent reports and papers, beginning with the launch meeting.
  • Identify the measures that must be made to comply with all existing regulatory obligations.
  • Make a practice of holding frequent weekly meetings to discuss issues, demonstrate progress, and provide a realistic estimate of the time and resources needed.
  • Make a plan for difficulties. New chemistry is inherently unexpected.
  • Don’t miss the kilo lab, which is full of surprises. Run the processes at least three times in increments of one kilogramme to twenty kilogrammes.
  • Look for a CDMO with a proven track record with the FDA and EMA.
  • Work with CDMOs that have solid raw materials and intermediates sourcing, as well as backups in case a supplier fails.

6. Methods for reducing elemental contaminants in API production:

Risk management requires reducing or eliminating these three types of impurities:

  • Elements of Class 1 Cd, Hg, and Pb are very hazardous metals with little or restricted application in API production.
  • Toxicity is determined by the mode of administration for Class 2A and 2B elements. The elements of Class 2A, Co, Ni, and V, have a high possibility of being found in the therapeutic product. Low abundance elements such as Ag, Au, Ir, Os, Pd, Pt, Rh, Ru, Se, and Tl may be eliminated from risk assessments unless they are actively included during pharmacological ingredient manufacturing.
  • For inhalation and parenteral routes, class 3 elements Ba, Cr, Cu, Li, Mo, Sb, and Sn require risk evaluation, whereas oral routes have comparatively low toxicity.

The following are some strategies for minimizing elemental impurities:

  • Examine the chemistry’s compatibility with the equipment that will be utilised; don’t put anything aggressive or corrosive in the line.
  • Maintain and check the equipment on a regular basis to avoid contamination from equipment failure.
  • Be aware of and prepare for the possibility of elemental contaminants entering the process.
  • Establish testing processes, and if contaminants are discovered to be out of specification, have protocols in place to eliminate or reduce them to acceptable levels.
  • Make complete drug substance purification a part of the process development.
  • Detecting trace metals using inductively coupled plasma (ICP) testing in a clean room during process development to discover where the metals are coming from, where they are collecting, and where they are being eliminated.
  • Perform ICP testing on a final material sample.
  • If a risk assessment reveals that the elemental impurity level is routinely over the control threshold, further measures should be implemented to ensure that the amount does not exceed the PDE for the dose form. These further controls might be implemented as in-process controls or as API requirements.
  • Begin elemental impurities risk management early as part of a raw materials quality campaign by seeking and reviewing information from suppliers, such as the Certificate of Analysis, to verify whether raw materials were tested for elemental impurities.

The most significant expenditures in API manufacturing are these three areas: chemistry, scale-up, and GMP plant time. 

With years of experience in designing, conceptualizing, building and qualifying a variety of API manufacturing units across various countries, Hvax Technologies has gained expertise in making your projects Viable- benefiting time, cost and quality.

Let us talk about your upcoming projects at

Leave a Comment on Things you need to know to set up an API Manufacturing Plant

Leave a Reply

Your email address will not be published. Required fields are marked *