Piramal Healthcare Ltd.
Piramal Healthcare Ltd

Headquarters
Piramal Towers, Peninsula Corporate Park, Lower Parel, Mumbai 400013, India

Location(s)
Morpeth (UK), Ahmedabad (India), Pithampur (India)

Years in Drug Formulation
4 Years

Spokesperson
Dr. R. Ananthanarayanan

Web site 

Company's role in drug discovery and developmnet
Piramal Healthcare is one of the few CMOs to help develop, scale up, and provide both clinical materials and commercial supply of drug products. The company is active in solid dose platform development and offers preformulations, formulations development, CTM supply, and clinical trials packaging/distribution from UK and India. The centers also support analytical development, validation, and stability studies. Piramal Healthcare has CROs in India and Romania, which can conduct BA/BE as well as Phase 1 – 4 clinical studies.

Development sites offer Phase 1 – 2 services and dovetail with FDA/MHRA -approved commercial sites, scaling up processes for Phase 3 +. They are supported by in-house QPs for supply of product in EU for clinical/commercial purposes.

Company's experience and expertise in drug formulation
Piramal Healthcare is active in solid dose development and CTM supply and has been operating as a CMO in this area for last 2.5 years. Teams in India and UK have a cross section of experience in controlled release and modified release drug development, led by scientists who have worked in NCE development with large pharma for over 10 years.

Piramal carries out development of hormonal solid dose in contained suites from its UK site and of high potent api drug products (>1 micrograms/m3 exposure) at its India development center. The company is able to develop OTC products from India and also has low RH suites (< 30% RH) to handle hygroscopic APIs.

Within technical platforms for drug development, Piramal has wet granulation (high shear, fluid bed processing) and dry processing (roller compaction, direct compression) equipment at our sites. All equipment for development is state-of-the art and is instrumented.

Relationship with pharma companies
Piramal Healthcare works on a contractual basis with pharma companies and does not itself take a stake in the drug. The company works with large pharma on the basis of dedicated teams (FTEs) for particular customers - where it is able to access multiple projects across different drug phases. One-off projects for pharma companies are also conducted on the basis of RFPs issued by the companies.

Piramal Healthcare offers a suite of services that can be bundled to meet customer request, while also routinely executing selected individual elements of the bundled offering of development+packaging+scale-up+commercial supply.

The company works with the customers to understand their needs for different clinical phases in terms of dose form and analytical method rigour. It then matches these with current regulatory requirements to arrive at a scope for the projects.

Factors critical for drug formulation
During Phase 1-2 studies the quantities of API are severely limited: developing an appropriate dose form therefore demands critical skills in understanding the physical characterization of API and thereby choose platforms without running many trials.

Often, due to physico-chemical factors, semi-automated operations are required and appropriate equipment as well as Quality SOPs needed to speed up the process. For this reason, Piramal Healthcare keeps separate set of SOPs for early phase and late phase projects.

In subsequent phases, statistical design of experiments to define parameters for formulations optimization is important and appropriate equipment to measure critical parameters, and set tighter boundaries for operation, is therefore important to ensure trouble-free scale up to commercial level.

Piramal uses instrumented equipment for development and commercial scale equipment with the same operating principles for scale up activity.

Scientific/business/regulatory trends impacting drug formulation
A very large number of drugs currently coming through the pipelines are of low solubility and low permeability. Formulations development using established techniques of use of different excipients, prodrug approaches, salt co-crystallisation etc. is becoming increasingly challenging, often requiring closer contact between API and Formulations development groups.

Additionally, customers do not want to lock into IP platforms in development and hence formulators have to be more creative in developing drugs. The safety/toxicity profile of drugs is also showing increasing potency, therefore requiring appropriate EHS systems in both lab and plant.

Large Pharma want to prioritise their early pipeline and with internal economic pressures are outsourcing more drug development activity – often to CMOs which can be more cost-effective. Small pharma would probably like Ph I/II work done in local regions but are increasingly more open to later phase work at approved facilities that offer cost and long term supply advantages –regardless of location.

With patient populations limited, a number of clinical trials for Cancer/CNS etc are becoming multi-national. Pharma companies are looking to partner with global CMOs while ensuring high quality, reliability and responsiveness on the CMO’s part. From a Regulatory perspective, fewer drugs are getting beyond Ph II and Ph I/II “fit for purpose” work for is therefore increasingly relevant.

Success story
Piramal Healthcare has worked with customers where we have been able to execute the drug substance GMP synthesis, drug product development and clinical supplies all from a single site for a Ph I study. The drug format was API in capsules.

During the Ph I dose escalation studies, the customer experienced greater tolerability of the drug and sought to increase the dosage. Additional formulations batches were therefore required and needed at the Clinical Trial Centres without slowing down patient recruitment.

Piramal was the partner for the drug product supply as well as packaging/labelling/distribution - and had inventory of the drug substance retained at the site.

The company was therefore able to take additional batches, carry out analysis, package and label and then supply the revised requirements in approximately four weeks This saved critical time for the customer – with the additional benefit of avoiding handoffs that would have been inherent in dealing with multiple partners.

How will roles of CROs and contract manufacturers change over the next few years?
As pharma in-house development/ CMC teams are reduced, CROs and CMOs will play greater role in ensuring safety, quality and regulatory appropriateness and compliance.

CROs/CMOs with capability for a cluster of activities will benefit over “specialists” offering more limited menus – likely motivating tie-ups with specialists for “add on” capabilities.

More block deals of dedicated FTEs for customers are likely with stricter IP controls within CMOs.