High quality standards, high production capacity and flexibility make Mipharm a Centre of Excellence for contract manufacturing and for developing new products and technology platforms

Giovanni Bernuzzi

Mipharm SpA was founded in 1998 by Mr Giuseppe G. Miglio thanks to a management buyout in Novartis Group. The company had worked as pharmaceutical company active in development, manufacturing and marketing of products manufactured at its plant in Milan (former Sandoz Italy facility) since 2009 when Mipharm has focused exclusively on contract manufacturing.

“Mipharm is a Center of Excellence in three main business areas (Contract Manufacturing, Special Services, Innovation and Technology) – says Mr Miglio – where the pharmaceutical company activity has merged with a modern and efficient production site since its beginning in 1998. In addition, Mipharm has set up an R&D service for the development of innovative products and a Special Services Business Unit to manage clinical trials logistics and to develop products in the generic (High Class Generics) and supergeneric area. Only a strategy that combine quality, customer service and other productive synergies allows to reach and consolidate a position of excellence in the competitive market of generic drugs. This is why in 2009 Mipharm has started a new business model, selling its commercial activities to Novartis group (that has a 10% stake in the capital share since 2002) and focusing its activity only to contract manufacturing”.

Which are the main Mipharm’s markets?

We are in all the five Continents. Our customers range from local mid-sized companies to large pharmaceutical multinationals such as Novartis Pharma, of which we are “preferred manufacturing supplier” for products sold worldwide.

Today pharmaceutical companies are focusing their efforts in the production of their “core” products and in new technologies; this trend creates new opportunities for contract manufacturing companies in classic pharmaceutical manufacturing, in supergenerics productions and in manufacturing niches where pharmaceutical companies prefer to avoid heavy capital investment. In this scenario, a contract manufacturer will be successful if it is settled in Countries where the highest level of pharmaceutical skills are combined with creativity, flexibility and customer-oriented service. This is what happens with Mipharm, where Swiss quality and Italian creativity merge themselves into a consolidated and multi-year capacity to supply Italian, European and global markets, such as USA, Japan, China and other Far East Countries.

How is Mipharm structured?

Mipharm is structured into three Divisions/Business Units: B.U.1- Manufacturing; B.U.3 – Special Services; B.U. 5 – Innovation and Technology. The production takes place in our manufacturing site in Milan, which has a production capacity of about 40 million units and is equipped with the most modern technologies; Mipharm has always invested significant resources in constant technology upgrading (e.g. the new of pharmaceutical products serialization equipment). The site has obtained four FDA approvals (last FDA inspection performed in September 2013) for the production departments for nasal sprays, Potent drugs, Sachets and Packaging Line. The Manufacturing Division has been developed starting from the former Sandoz production site and today can manufacture and package a broad spectrum of products and pharmaceutical forms in compliance with European and U.S. FDA cGMP standards, such as nasal spray, potent drug, sachets, creams, suppositories (Alu-Alu, PVC peel-off), slow-release pellets, by using several technologies like granulation, tabletting, film coating, sugar coating, pellet coating, compounding and filling of oral and nasal spray solutions, preparation and packaging of creams and gels, powders packaging into pouches, solid dosage form into blister (Alu/Alu and PVC film), or tubes and bottle, and packaging of bottles, blisters and nasal sprays.

We can start the tour in the Oral Solid Department. It had been reshaped and refurbished several times to house new equipment and to insert a special area dedicated to the pellets filming equipment with organic solvents recovery. The department includes two Class 10,000 oral solutions filling lines (one for gas-protected and the other for plain oral solutions) with equipment and processes validated and complying with FDA standards.

The department has two suppository production lines (Alu/Alu strip and PVC/PE strip) and the whole production cycle, beginning from ingredients mixing up to final packaging, is fully integrated and automated in order to guarantee a continuous reproducibility of the operation parameters and very short production times.

The Cream Department is equipped with a 600-liter turbo emulsifier and provides maximum flexibility in dosage and tube size.

The Packaging Department is provided with lines equipped with advanced control systems (single filled alveolus monitoring, bar code readers etc.) and is dedicated to packaging solid forms in blister packs (PVC/Alu, Alu/Alu, PET/Alu, PP/Alu, PVC/ACLAR ), bottles and tubes. Finally, there are our crowning achievements, the four FDA approved Departments:Nasal sprays, Potent drugs, Sachet and Packaging Line.

How are they equipped?

The Nasal Spray Department has two lines one with a screwed dosage system and the other with a clamped or pressed dosage system. Both lines have a continuous monitoring of closure system torque. The filling phase takes place in Class 10,000 conditions.

The operations in the Potent drugs Department take place in an entirely segregated area with a high efficiency dust emission control system. The Department’s equipment allows the whole production and packaging cycle for solid oral dosage forms, from granulation to final packaging of the blister cards in cartons. It is also possible to obtain special packaging presentations, such as child-resistant presentations blister and 5 layer film blister card.

The Sachet Department has four lines (two compounding and mixing lines and two filling and packaging lines) that allows a great flexibility in dosage volumes and sachet sizes. The power handling takes place in a fully enclosed environment.

What is Mipharm for its customers?

Mipharm is a customer’s partner able provide the highest answers not only relating to the current state of art, but also cost competitive, quick and timely, flexible and focused on customer’s needs. To achieve its operational excellence, Mipharm adopts a problem-solving approach called IQP, based on Innovation (Value creation), Quality (Value attainment), Productivity (Value retention). The Lean Manufacturing Methodologies, a fundamental IPQ tool, have been introduced in our company since 2004; gradually they have involved the most important production lines, increasing the OAE (Active Overall Effectiveness) indices.  Our work’s goal is the complete customer’s satisfaction, in order to establish strong and lasting relationships based on the achieved results.

For this reason, since our beginning, we have given a particular attention to technological transfer activities through a careful evaluation of the registration dossier, as we think that this step is crucial to verify the full adherence to what is reported in the dossier. To do this we adopt a detailed GAP analysis on production and analytical methods. The validation activities performed on the transfer assurance us that of our products is fully complying with the quality requirements of the dossier. At each stage of the production cycle, from initial analysis to production and delivery of the product finished and packaged, the customer is supported by a full-service that involve all our functions and divisions, covering each technical, regulatory and manufacturing aspect of pharmaceutical production.

Which are the services offered by the Special Services B.U.?

The services provided are mainly in three areas: new product pharmaceutical development, Quality Assurance and Quality Control services, clinical trial logistics management. With regard to the first, we offer a full partnership in the product development process (formulation studies, manufacturing of laboratory and pilot scale batches, industrial scale-up and validation batches, manufacturing process optimization, technical dossiers for registration dossier). The QA-QC services include chemical and microbiological tests on raw materials and finished products, test on environmental hygiene, tests on the packaging material, stability studies, development and validation of analytical methods in accordance with ICH guidelines. The B.U. can support pharmaceutical companies and CROs in managing clinical trial logistics, prepare active drug products and placebo (manufacturing, analytical testing, single or double-blind packaging) in full compliance with cGMP and GLP, delivery the samples to the clinical centers and collection of unused material at the end of the study.

What about those offered by the Innovation and Technology B.U.?

This B.U. focuses on patented proprietary technology platforms in order to reach new standards of tolerability, efficacy and delivery by using new or already known active ingredients. In particular, it focuses on studying innovative carrier to increase the effectiveness and to improve compliance of active ingredients already widely used. Mipharm is able to develop new products based on different technological platforms, such Miphargel® and Moussina®, a cutaneous foam in constant delivery, propellant free, which acts as a powerful carrier in delivering active ingredients. The vaginal delivery system Miphargel® is so innovative to obtain several patents: European in 2007, Chinese in 2009, Japanise in 2011 and U.S. in 2014.


Pharmaceutical products serialization

The serialization of pharmaceutical products is an up-to-date hot topic, which arises from the need to trace unambiguously medicinal products in order to combat counterfeiting and to ensure safety and traceability of each product throughout the whole supply chain up to the end user. Mipharm has set up a system (equipment and software) that can serialize some of products of its lines and, together with one of its major customer, has launched a joint project to comply with Chinese regulations on serialization (enacted starting from 1st January 2014 ) in order to export to China a product packaged at the Mipharm plant of Milan. This know-how will be essential to export to other countries that will implement serialization in the next future such as California in 2015 and Europe in 2016. The scope of the project is to implement a quality control system using electronic bar codes to ensure product traceability, documentation and standard information that must then be cross-checked to verify the electronic files between the client and the Chinese Health Authority. This further step towards greater safety and production quality confirms Mipharm as cutting edge company in addressing the new challenges of the pharmaceutical market, continuously innovating and doing it with the best suppliers.


The Company

Founded in Milan in 1998, Mipharm S.p.A. focuses only on contract manufacturing. It is structured in three Divisions/Business Units: Manufacturing, Special Services, Innovation and Technology. Present on several worldwide markets, operates in compliance with European and U.S. FDA cGMP standards for production and packaging of solid oral dosage forms, coated pellets, oral solutions, nasal spray solutions, semi-solid dosage forms, suppositories and creams.